Substituted 5,6,7,8-Tetrahydro-pyrido[4,3-d]pyrimidine-2-yl Compounds and 5,6,7,8-Tetrahydro-quinazoline-2-yl Compounds

ABSTRACT

Substituted 5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl and 5,6,7,8-tetrahydro-quinazolin-2-yl compounds, corresponding to formula I 
     
       
         
         
             
             
         
       
     
     processes for the production thereof, pharmaceutical preparations containing these compounds the use thereof for the production of pharmaceutical preparations and related method of treating or inhibiting certain disorders or conditions, including pain.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a division of co-pending application Ser. No. 11/588,238, filed Oct. 27, 2006, now U.S. Pat. No. ______, which in turn is a continuation of International patent application Serial No. PCT/EP2005/004489 filed Apr. 27, 2005 designating the United States of America, and published in German on Nov. 10, 2005 as WO 2005/105759, which claims benefit of Federal Republic of Germany patent application no. DE 10 2004 020 908.1, filed Apr. 28, 2004, the entire disclosures of which are incorporated herein in their entirety.

FIELD OF THE INVENTION

The present invention relates to substituted 5,6,7,8-tetrahydro-pyrido[4,3-d]-pyrimidin-2-yl and 5,6,7,8-tetrahydroquinazolin-2-yl compounds, processes for the production thereof, pharmaceutical formulation containing these compounds, methods of producing such pharmaceutical formulation, and related methods of treating or inhibiting certain conditions or disorders, including pain.

BACKGROUND OF THE INVENTION

Pain is one of the basic clinical symptoms. There is a worldwide need for effective pain treatments. The urgency of the requirement for therapeutic methods for providing tailored and targeted treatment of chronic and non-chronic pain, this being taken to mean pain treatment which is effective and satisfactory from the patient's standpoint, is also evident from the large number of scientific papers relating to applied analgesia and to basic nociception research which have appeared in recent times.

Conventional opioids, such as for example morphine, are effective in the treatment of severe to very severe pain, but they often lead to unwanted accompanying symptoms, such as for example respiratory depression, vomiting, sedation, constipation or the development of tolerance. Moreover, they are frequently insufficiently effective in the case of neuropathic pain, suffered in particular by tumor patients.

SUMMARY OF THE INVENTION

One object of the present invention was accordingly to provide novel compounds which are suitable in particular as pharmaceutical active ingredients in pharmaceutical preparations, preferably in pharmaceutical preparations for the prevention and/or treatment of pain, in particular acute pain, chronic pain, neuropathic or visceral pain.

It has now surprisingly been found that the substituted 5,6,7,8-tetrahydro-pyrido-[4,3-d]pyrimidin-2-yl and 5,6,7,8-tetrahydro-quinazolin-2-yl compounds of the general formula I stated hereinafter are suitable for noradrenalin receptor regulation, in particular for inhibiting noradrenalin reuptake (noradrenalin uptake), for 5-HT receptor regulation, in particular for inhibiting 5-hydroxy tryptophan reuptake (5-HT uptake), for mGluR5 receptor regulation and/or for batrachotoxin (BTX) receptor regulation and may therefore be used in particular as pharmaceutical active ingredients in pharmaceutical preparations for preventing and/or treating disorders or diseases associated with these receptors or processes.

The present invention accordingly provides substituted 5,6,7,8-tetrahydro-pyrido-[4,3-d]pyrimidin-2-yl and 5,6,7,8-tetrahydroquinazolin-2-yl compounds of the general formula I,

in which

X denotes a C(H)(NHR²) group or an NR^(2a) group,

R¹ denotes a —C(═O)—R³ group or a —C(═O)—O—R⁴ group,

R², R^(2a), mutually independently, in each case denote a —C(═O)—R⁵ group or an —S(═O)₂—R⁶ group,

R³ denotes a linear or branched, unsubstituted or at least monosubstituted, saturated or unsaturated aliphatic residue, optionally comprising at least one heteroatom as a chain link, an unsubstituted or at least monosubstituted, saturated or unsaturated cycloaliphatic residue, optionally comprising at least one heteroatom as a ring member, which residue may be attached via a linear or branched, unsubstituted or at least monosubstituted alkylene group, optionally comprising at least one heteroatom as a chain link, or an unsubstituted or at least monosubstituted aryl or heteroaryl residue, which may be attached via a linear or branched, unsubstituted or at least monosubstituted alkylene group,

R⁴ denotes an unsubstituted or at least monosubstituted aryl or heteroaryl residue, which may be attached via a linear or branched, unsubstituted or at least monosubstituted alkylene group,

R⁵ denotes a linear or branched, unsubstituted or at least monosubstituted, saturated or unsaturated aliphatic residue, optionally comprising at least one heteroatom as a chain link,

an unsubstituted or at least monosubstituted, saturated or unsaturated cycloaliphatic residue, optionally comprising at least one heteroatom as a ring member, which residue may be attached via a linear or branched, unsubstituted or at least monosubstituted alkylene group, optionally comprising at least one heteroatom as a chain link, and/or be fused with an unsubstituted or at least monosubstituted, mono- or polycyclic ring system,

an unsubstituted or at least monosubstituted aryl or heteroaryl residue, which may be attached via a linear or branched, unsubstituted or at least monosubstituted alkylene, alkenylene or alkynylene group, optionally comprising at least one heteroatom as a chain link and/or be fused with an unsubstituted or at least monosubstituted, mono- or polycyclic ring system,

a —C(═O)—R⁷ residue, which may be attached via a linear or branched, unsubstituted or at least monosubstituted alkylene group,

a —C(═O)—R⁸ residue, which may be attached via a linear or branched, unsubstituted or at least monosubstituted alkylene group, or

an —N(H)—C(═O)—O—R⁹ residue, which may be attached via a linear or branched, unsubstituted or at least monosubstituted alkylene group, optionally comprising at least one —N(H)—C(═O) or at least one —C(═O)—N(H) grouping as a chain link,

R⁶ denotes a group —NR¹⁰R¹¹,

a linear or branched, unsubstituted or at least monosubstituted, saturated or unsaturated aliphatic residue, optionally comprising at least one heteroatom as a chain link,

an unsubstituted or at least monosubstituted, saturated or unsaturated cycloaliphatic residue, optionally comprising at least one heteroatom as a ring member, optionally fused with an unsubstituted or at least monosubstituted mono- or polycyclic ring system, which residue may be attached via a linear or branched, unsubstituted or at least monosubstituted alkylene group, optionally comprising at least one heteroatom as a chain link and/or be bridged with a linear or branched alkylene group, or

an unsubstituted or at least monosubstituted aryl or heteroaryl residue, which may be attached via a linear or branched, unsubstituted or at least monosubstituted alkylene group and/or be fused with an unsubstituted or at least monosubstituted mono- or polycyclic ring system,

R⁷ denotes a linear or branched, unsubstituted or at least monosubstituted alkyl residue, an unsubstituted or at least monosubstituted aryl or heteroaryl residue, an unsubstituted or at least monosubstituted, saturated or unsaturated cycloaliphatic residue, optionally comprising at least one heteroatom as a ring member, which residue may be fused with an unsubstituted or at least monosubstituted mono- or polycyclic ring system, or an —NR^(7a)R^(7b) residue, in which the residues R^(7a) and R^(7b), identical or different, in each case denote a linear or branched alkyl residue,

R⁸ denotes a linear or branched, unsubstituted or at least monosubstituted alkyl residue or an unsubstituted or at least monosubstituted aryl or heteroaryl residue, optionally attached via a linear or branched alkylene group,

R⁹ denotes a linear or branched, unsubstituted or at least monosubstituted alkyl residue, an unsubstituted or at least monosubstituted aryl or heteroaryl residue, optionally attached via a linear or branched alkylene group, or an unsubstituted or at least monosubstituted, saturated or unsaturated cycloaliphatic residue, which may be fused with at least one unsubstituted or at least monosubstituted mono- or polycyclic ring system, and

R¹⁰, R¹¹, identical or different, in each case denote a linear or branched alkyl residue,

in each case optionally in the form of one of the pure stereoisomers thereof, in particular enantiomers or diastereomers, the racemates thereof or in the form of a mixture of stereoisomers, in particular the enantiomers and/or diastereomers, in any desired mixing ratio, or in each case in the form of corresponding salts or in each case in the form of corresponding solvates.

If one or more of the substituents R³ and R⁵-R⁹ denote a saturated or unsaturated aliphatic residue, i.e. an alkyl, alkenyl or alkynyl residue, which is mono- or polysubstituted, for example 1, 2, 3, 4, 5, 6, 7, 8 or 9 times, the substituents thereof may, in each case mutually independently, preferably be selected from the group consisting of F, Cl, Br, —OH, —SH and —NH₂. Alkenyl residues comprise at least one C—C double bond and alkynyl residues at least one C—C triple bond.

Examples of suitable alkyl, alkenyl and alkynyl residues, which may be mono- or polysubstituted, are methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, n-pentyl, iso-pentyl, neopentyl, n-hexyl, 2-hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl, —C(H)(C₂H₅)₂, —C(H)(n-C₃H₇)₂, —CH₂—CH₂—C(H)(CH₃)—(CH₂)₃—CH₃, vinyl, ethynyl, propenyl, allyl, propynyl, butenyl, butynyl, pentenyl, pentynyl, hexenyl, hexynyl, —CH═CH—CH═CH—CH₃ and —CH₂—CH₂—CH═CH₂.

If one or more of the substituents R³, R⁵ and R⁶ denote a saturated or unsaturated aliphatic residue, i.e. an alkyl, alkenyl or alkynyl residue, which comprises one or more, for example 1, 2, 3, 4 or 5, heteroatoms as chain link(s), these heteroatoms, in each case mutually independently, may preferably be selected from the group consisting of oxygen, sulfur and nitrogen (NH). Preferably, these heteroatoms are located in a non-terminal position of the respective residue. Residues such as —CH₂—CH₂—S—CH₃, —CH₂—O—CH₂—CH₂—O—CH₃, —CH₂—O—CH₃ or —CH₂—CH₂—O—CH₃ may be mentioned by way of example.

If one or more of the substituents R³, R⁵-R⁷ and R⁹ denote a cycloaliphatic residue or comprises a cycloaliphatic residue, which is mono- or polysubstituted, for example 1, 2, 3, 4 or 5 times, the substituents thereof may, in each case mutually independently, preferably be selected from the group consisting of —C₁₋₅ alkyl, —C(═O)—O—C₁₋₅-alkyl, —C(═O)—CF₃, —S(═O)₂—C₁₋₅-alkyl, —S(═O)₂-phenyl, oxo (═O) and phenyl, wherein the C₁₋₅ alkyl residue may in each case be linear or branched and the phenyl residue may in each case be mono- or polysubstituted, for example 1, 2, 3, 4 or 5 times, identically or differently, with a substituent selected from the group consisting of F, Cl, Br and I. Particularly preferably, the substituents, in each case mutually independently, may be selected from the group consisting of —C(═O)—O-tert-butyl, —C(═O)—CF₃, —S(═O)₂-methyl, —S(═O)₂-phenyl, oxo, and phenyl, wherein the phenyl residue may in each case be mono- or polysubstituted, for example 1, 2, 3, 4 or 5 times, identically or differently, with a substituent selected from the group consisting of F, Cl and Br.

If the cycloaliphatic residues comprise one or more, for example 1, 2 or 3, heteroatoms as ring members, these, in each case mutually independently, may preferably be selected from the group consisting of nitrogen, oxygen and sulfur.

Examples of suitable cycloaliphatic residues, which may be mono- or polysubstituted, are cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclopentenyl, cyclohexenyl, cycloheptenyl, cyclooctenyl, imidazolidinyl, tetrahydrofuranyl (tetrahydrofuryl), piperidinyl, piperazinyl, morpholinyl and dithiolanyl.

If one or more of the substituents R³-R⁹ denote an aryl or heteroaryl residue or comprise an aryl or heteroaryl residue, which is mono- or polysubstituted, for example 1, 2, 3, 4 or 5 times, the substituents thereof may, in each case mutually independently, preferably be selected from the group consisting of halogen, —CN, —NO₂, —OH, —SH, C₁₋₅ alkyl, C₁₋₅ alkoxy, —S—C₁₋₅-alkyl, —CF₃, —CHF₂, —CH₂F, —O—CF₃, —O—CHF₂, —O—CH₂F, —C(═O)—CF₃, —S—CF₃, —S—CHF₂, —S—CH₂F, —S(═O)₂-phenyl, —S(═O)₂—C₁₋₅ alkyl, N(C₁₋₅alkyl)(C₁₋₅-alkyl), —C(═O)—O—C₁₋₅-alkyl, —CH₂—O—C(═O)-phenyl, —O—C(═O)-phenyl, —NH—C(═O)—C₁₋₅-alkyl, —C≡C-phenyl, —C≡C-naphthyl, —C≡C-pyrrolyl, —C≡C-indolyl, —C≡C-furyl (—C≡C-furanyl), —C≡C-benzo[b]furanyl, —C≡C-thienyl (—C≡C-thiophenyl), —C≡C-benzo[b]thienyl, —C≡C-pyrazolyl, —C≡C-imidazolyl, —C≡C-thiazolyl, —C≡C-thiadiazolyl, —C≡C-triazolyl, —C≡C-oxazolyl, —C≡C-isoxazolyl, —C≡C-pyridinyl, —C≡C-pyridazinyl, —C≡C-pyrimidinyl, —C≡C-pyrazinyl, —C≡C-pyranyl, —C≡C-indazolyl, —C≡C-purinyl, —C≡C-indolizinyl, —C≡C-quinolinyl, —C≡C-isoquinolinyl, —C≡C-quinazolinyl, pyrazolyl, phenyl, furyl (furanyl), thiadiazolyl, thiophenyl (thienyl), phenoxy and benzyl, wherein the cyclic substituents may themselves in each case be mono- or polysubstituted, for example 1, 2, 3, 4 or 5 times, identically or differently, with a substituent selected from the group consisting of F, Cl, Br, I.

Particularly preferably, the substituents, in each case mutually independently, may be selected from the group consisting of F, Cl, Br, I, —CN, —NO₂, —OH, —SH, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, n-pentyl, neopentyl, methoxy, ethoxy, n-propoxy, iso-propoxy, n-butyloxy, iso-butyloxy, sec-butyloxy, tert-butyloxy, —S-methyl, —S-ethyl, —CF₃, —CHF₂, —CH₂F, —O—CF₃, —O—CHF₂, —O—CH₂F, —C(═O)—CF₃, —S—CF₃, —S—CHF₂, —S—CH₂F, —S(═O)₂-phenyl, pyrazolyl, phenyl, —N(CH₃)₂, —N(C₂H₅)₂, —CH₂—O—C(═O)-phenyl, —C(═O)—O—CH₃, —C(═O)—O—C₂H₅, —NH—C(═O)—CH₃, —O—C(═O)-phenyl, —C≡C-phenyl, —C≡C-furyl (—C≡C-furanyl), —C≡C-thiadiazolyl, —C≡C-thiophenyl (—C≡C-thienyl), phenyl, furyl (furanyl), thiadiazolyl, thiophenyl (thienyl), phenoxy and benzyl, wherein the cyclic substituents may themselves in each case be mono- or polysubstituted, for example 1, 2, 3, 4 or 5 times, identically or differently, with a substituent selected from the group consisting of F, Cl, Br, I.

Examples of suitable aryl residues which may be mentioned are phenyl, 1-naphthyl and 2-naphthyl.

If one or more of the substituents R³-R⁹ denote a heteroaryl residue or comprise a heteroaryl residue, the heteroatom(s) thereof may, in each case mutually independently, preferably be selected from the group consisting of oxygen, sulfur and nitrogen. For example, the heteroaryl residues may comprise 1, 2, 3, 4 or 5 heteroatoms.

Suitable heteroaryl residues which may be mentioned are, for example, pyrrolyl, indolyl, furyl (furanyl), benzo[b]furanyl, thienyl (thiophenyl), benzo[b]thienyl, pyrazolyl, imidazolyl, thiazolyl, thiadiazolyl, triazolyl, oxazolyl, isoxazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, pyranyl, indazolyl, purinyl, indolizinyl, quinolinyl, isoquinolinyl and quinazolinyl.

For the purposes of the present invention, a mono- or polycyclic ring system should be understood to mean mono- or polycyclic hydrocarbon residues which may be saturated, unsaturated or aromatic and optionally comprise one or more, for example 1, 2, 3, 4 or 5, heteroatoms as ring members. Such a mono- or polycyclic ring system may, for example, be fused (anellated) with a cycloaliphatic residue, an aryl residue or a heteroaryl residue.

If a polycyclic ring system is present, the different rings may, in each case mutually independently, exhibit a different degree of saturation, i.e. be saturated, unsaturated or aromatic. The heteroatoms of each ring may, in each case identically or differently, preferably be selected from the group consisting of oxygen, nitrogen and sulfur. Preferably, the respective rings of the mono- or polycyclic ring system are 5- or 6-membered. Preferably, polycyclic ring systems should be understood to mean bicyclic ring systems.

If one or more of the substituents R⁵, R⁶, R⁷ and R⁹ comprise a monocyclic or polycyclic ring system which is mono- or polysubstituted, for example 1, 2, 3, 4 or 5 times, the substituents thereof may, in each case mutually independently, preferably be selected from the group consisting of halogen, —CN, —NO₂, —OH, —SH, C₁₋₅ alkyl, C₁₋₅ alkoxy, —S—C₁₋₅-alkyl, —CF₃, —CHF₂, —CH₂F, —O—CF₃, —O—CHF₂, —O—CH₂F, —C(═O)—CF₃, —S—CF₃, —S—CHF₂, —S—CH₂F, —S(═O)₂-phenyl, —S(═O)₂—C₁₋₅-alkyl, N(C₁₋₅alkyl)(C₁₋₅ alkyl), —C(═O)—O—C₁₋₅-alkyl, —CH₂—O—C(═O)-phenyl, —O—C(═O)-phenyl, —NH—C(═O)—C₁₋₅-alkyl, —C≡C-phenyl, —C≡C-naphthyl, —C≡C-pyrrolyl, —C≡C-indolyl, —C≡C-furyl (—C≡C-furanyl), —C≡C-benzo[b]furanyl, —C≡C-thienyl (—C≡C-thiophenyl), —C≡C-benzo[b]thienyl, —C≡C-pyrazolyl, —C≡C-imidazolyl, —C≡C-thiazolyl, —C≡C-thiadiazolyl, —C≡C-triazolyl, —C≡C-oxazolyl, —C≡C-isoxazolyl, —C≡C-pyridinyl, —C≡C-pyridazinyl, —C≡C-pyrimidinyl, —C≡C-pyrazinyl, —C≡C-pyranyl, —C≡C-indazolyl, —C≡C-purinyl, —C≡C-indolizinyl, —C≡C— quinolinyl, —C≡C-isoquinolinyl, —C≡C-quinazolinyl, pyrazolyl, phenyl, furyl (furanyl), thiadiazolyl, thiophenyl (thienyl), phenoxy and benzyl, wherein the cyclic substituents may themselves in each case be mono- or polysubstituted, for example 1, 2, 3, 4 or 5 times, identically or differently, with a substituent selected from the group consisting of F, Cl, Br, I. Particularly preferably, the substituents, in each case mutually independently, may be selected from the group consisting of F, Cl, Br, I, —CN, —NO₂, —OH, —SH, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, n-pentyl, neopentyl, methoxy, ethoxy, n-propoxy, iso-propoxy, n-butyloxy, iso-butyloxy, sec-butyloxy, tert-butyloxy, —S-methyl, —S-ethyl, —CF₃, —CHF₂, —CH₂F, —O—CF₃, —O—CHF₂, —O—CH₂F, —C(═O)—CF₃, —S—CF₃, —S—CHF₂, —S—CH₂F, —S(═O)₂-phenyl, pyrazolyl, phenyl, —N(CH₃)₂, —N(C₂H₅)₂, —CH₂—O—C(═O)-phenyl, —C(═O)—O—CH₃, —C(═O)—O—C₂H₅, —NH—C(═O)—CH₃, —O—C(═O)-phenyl, furyl (furanyl), thiadiazolyl, thiophenyl (thienyl), phenoxy and benzyl, wherein the cyclic substituents may themselves in each case be mono- or polysubstituted, for example 1, 2, 3, 4 or 5 times, identically or differently, with a substituent selected from the group consisting of F, Cl, Br, I.

If one of the above-stated substituents R³-R⁶ comprises a linear or branched alkylene, alkenylene or alkynylene group, which is mono- or polysubstituted, for example 1, 2, 3, 4 or 5 times, the substituents thereof may, in each case mutually independently, preferably be selected from the group consisting of F, Cl, Br, hydroxy and unsubstituted phenyl.

If the alkylene, alkenylene or alkynylene group comprises one or more, for example 1, 2, 3, 4 or 5, heteroatoms as chain link(s), these may preferably be selected from the group consisting of oxygen, sulfur and nitrogen (NH).

Examples which may be stated are alkylene, alkenylene or alkynylene groups such as —(CH₂)—, —(CH₂)₂—, —(CH₂)₃—, —(CH₂)₄—, —(CH₂)₅—, —C(H)(CH₂phenyl), —C(H)(phenyl), —C(H)(C)(H)(CH₃)₂), —C(C₂H₅)(H)—, —(CH₂)—O—, —(CH₂)₂—O—, —(CH₂)₃—O—, —(CH₂)₄—O—, —O—(CH₂)—, —O—(CH₂)₂—, —O—(CH₂)₃—, —O—(CH₂)₄—, —C(C₂H₅)(H)—O—, —O—C(C₂H₅)(H)—, —CH₂—O—CH₂—, —CH₂—S—CH₂—, —C(CH₃)₂—, —C(H)(CH₃)—, —CH═CH— and —C≡C—.

Preferred substituted 5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl and 5,6,7,8-tetrahydro-quinazolin-2-yl compounds of the above-stated general formula I are those

in which

X denotes a C(H)(NHR²) group or an NR^(2a) group,

R¹ denotes a —C(═O)—R³ group or a —C(═O)—O—R⁴ group,

R², R^(2a), mutually independently, in each case denote a —C(═O)—R⁵ group or an —S(═O)₂—R⁶ group,

R³ denotes a linear or branched, unsubstituted or at least monosubstituted, saturated or unsaturated aliphatic C₁₋₈ residue, optionally comprising at least one heteroatom as a chain link, an unsubstituted or at least monosubstituted, saturated or unsaturated 3- to 8-membered cycloaliphatic residue, optionally comprising at least one heteroatom as a ring member, which residue may be attached via a linear or branched, unsubstituted or at least monosubstituted C₁₋₃ alkylene group, optionally comprising at least one heteroatom as a chain link, or an unsubstituted or at least monosubstituted 5- to 14-membered aryl or heteroaryl residue, which may be attached via a linear or branched, unsubstituted or at least monosubstituted C₁₋₃ alkylene group,

R⁴ denotes an unsubstituted or at least monosubstituted 5- to 14-membered aryl or heteroaryl residue, which may be attached via a linear or branched, unsubstituted or at least monosubstituted C₁₋₃ alkylene group,

R⁵ denotes a linear or branched, unsubstituted or at least monosubstituted, saturated or unsaturated aliphatic C₁₋₁₀ residue, optionally comprising at least one heteroatom as a chain link,

an unsubstituted or at least monosubstituted, saturated or unsaturated 3- to 8-membered cycloaliphatic residue, optionally comprising at least one heteroatom as a ring member, which residue may be attached via a linear or branched, unsubstituted or at least monosubstituted C₁₋₆ alkylene group, optionally comprising at least one heteroatom as a chain link and/or be fused with an unsubstituted or at least monosubstituted, mono- or polycyclic ring system,

an unsubstituted or at least monosubstituted 5- to 14-membered aryl or heteroaryl residue, which may be attached via a linear or branched, unsubstituted or at least monosubstituted C₁₋₆ alkylene, C₂₋₆ alkenylene or C₂₋₆ alkynylene group, optionally comprising at least one heteroatom as a chain link and/or be fused with an unsubstituted or at least monosubstituted, mono- or polycyclic ring system,

a —C(═O)—R⁷ residue, which may be attached via a linear or branched, unsubstituted or at least monosubstituted C₁₋₃ alkylene group,

a —C(═O)—R⁸ residue, which may be attached via a linear or branched, unsubstituted or at least monosubstituted C₁₋₃ alkylene group, or

an —N(H)—C(═O)—O—R⁹ residue, which may be attached via a linear or branched, unsubstituted or at least monosubstituted C₁₋₈ alkylene group, optionally comprising at least one —N(H)—C(═O) or at least one —C(═O)—N(H) grouping as a chain link,

R⁶ denotes a group —NR¹⁰R¹¹,

a linear or branched, unsubstituted or at least monosubstituted, saturated or unsaturated aliphatic C₁₋₁₀ residue, optionally comprising at least one heteroatom as a chain link,

an unsubstituted or at least monosubstituted, saturated or unsaturated cycloaliphatic residue, optionally comprising at least one heteroatom as a ring member, optionally fused with an unsubstituted or at least monosubstituted mono- or polycyclic ring system, which residue may be attached via a linear or branched, unsubstituted or at least monosubstituted C₁₋₆ alkylene group, optionally comprising at least one heteroatom as a chain link and/or be bridged with a linear or branched C₁₋₆ alkylene group, or

an unsubstituted or at least monosubstituted 5- to 14-membered aryl or heteroaryl residue, which may be attached via a linear or branched, unsubstituted or at least monosubstituted C₁₋₆ alkylene group and/or be fused with an unsubstituted or at least monosubstituted mono- or polycyclic ring system,

R⁷ denotes a linear or branched, unsubstituted or at least monosubstituted C₁₋₃ alkyl residue, an unsubstituted or at least monosubstituted 5- to 14-membered aryl or heteroaryl residue, an unsubstituted or at least monosubstituted, saturated or unsaturated 5-, 6- or 7-membered cycloaliphatic residue, optionally comprising at least one heteroatom as a ring member, which residue may be fused with an unsubstituted or at least monosubstituted mono- or polycyclic ring system, or denotes an —NR^(7a)R^(7b) residue, in which the residues R^(7a) and R^(7b), identical or different, in each case denote a linear or branched C₁₋₅ alkyl residue,

R⁸ denotes a linear or branched, unsubstituted or at least monosubstituted C₁₋₃ alkyl residue or an unsubstituted or at least monosubstituted 5- or 6-membered aryl or heteroaryl residue, optionally attached via a linear or branched C₁₋₃ alkylene group,

R⁹ denotes a linear or branched, unsubstituted or at least monosubstituted C₁₋₃ alkyl residue, an unsubstituted or at least monosubstituted 5- or 6-membered aryl or heteroaryl residue, optionally attached via a linear or branched C₁₋₃ alkylene group, or an unsubstituted or at least monosubstituted, saturated or unsaturated 5- or 6-membered cycloaliphatic residue, which may be fused with at least one unsubstituted or at least monosubstituted mono- or polycyclic ring system, and,

R¹⁰, R¹¹, identical or different, in each case denote a linear or branched C₁₋₅ alkyl residue,

in each case optionally in the form of one of the pure stereoisomers thereof, in particular enantiomers or diastereomers, the racemates thereof or in the form of a mixture of stereoisomers, in particular the enantiomers and/or diastereomers, in any desired mixing ratio, or in each case in the form of corresponding salts or in each case in the form of corresponding solvates.

Also preferred are substituted 5,6,7,8-tetrahydro-pyrido[4,3-(d)]pyrimidin-2-yl and 5,6,7,8-tetrahydro-quinazolin-2-yl compounds of the above-stated general formula I, in which R³ denotes a linear or branched, unsubstituted or at least monosubstituted C₁₋₈ alkyl residue, optionally comprising one or more oxygen atoms and/or one or more NH groups as chain link(s), an unsubstituted or at least monosubstituted, saturated or unsaturated 5-, 6- or 7-membered cycloaliphatic residue, optionally comprising at least one heteroatom as a ring member, which residue may be attached via a linear or branched, unsubstituted or at least monosubstituted C₁₋₃ alkylene group, optionally comprising at least one heteroatom as a chain link, or an unsubstituted or at least monosubstituted phenyl residue, thiophenyl residue (thienyl residue), furanyl residue (furyl residue), pyridinyl residue or naphthyl residue, which may be attached via a linear or branched, unsubstituted or at least monosubstituted C₁₋₃ alkylene group,

preferably a methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl or tert-butyl residue, an unsubstituted, saturated or unsaturated 5-, 6- or 7-membered cycloaliphatic residue, optionally comprising one or more oxygen atoms and/or one or more nitrogen atoms as ring member(s), which residue may be attached via a —(CH₂)—, —(CH₂)₂ or —(CH₂)₃ group, or a phenyl residue, thiophenyl residue (thienyl residue), furanyl residue (furyl residue), pyridinyl residue or naphthyl residue, which may be attached via a —(CH₂)—, —(CH₂)₂ or —(CH₂)₃ group and/or be mono- or polysubstituted, identically or differently, with a substituent selected from the group consisting of methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, methoxy, ethoxy, n-propoxy, iso-propoxy, n-butoxy, iso-butoxy, sec-butoxy, tert-butoxy, F, Cl, Br, I, —CN and —CF₃,

and the respective remaining residues X, R¹, R², R^(2a) and R⁴ to R¹¹ have the above-stated meaning, in each case optionally in the form of one of the pure stereoisomers thereof, in particular enantiomers or diastereomers, the racemates thereof or in the form of a mixture of stereoisomers, in particular the enantiomers and/or diastereomers, in any desired mixing ratio, or in each case in the form of corresponding salts, or in each case in the form of corresponding solvates.

Also preferred are substituted 5,6,7,8-tetrahydro-pyrido[4,3-d]-pyrimidin-2-yl and 5,6,7,8-tetrahydro-quinazolin-2-yl compounds of the above-stated general formula I, in which the residue R⁴ denotes a phenyl residue optionally attached via a —(CH₂), —(CH₂)₂ or —(CH₂)₃ bridge, wherein the phenyl ring, unsubstituted or at least monosubstituted, identical or different, may be substituted with a substituent selected from among the group consisting of methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, methoxy, ethoxy, n-propoxy, iso-propoxy, n-butoxy, iso-butoxy, sec-butoxy, tert-butoxy, F, Cl, Br, I, —CN and —CF₃,

preferably an unsubstituted benzyl residue,

and the respective remaining residues X, R¹, R², R^(2a), R³ and R⁵ to R¹¹ have the above-stated meaning, in each case optionally in the form of one of the pure stereoisomers thereof, in particular enantiomers or diastereomers, the racemates thereof or in the form of a mixture of stereoisomers, in particular the enantiomers and/or diastereomers, in any desired mixing ratio, or in each case in the form of corresponding salts, or in each case in the form of corresponding solvates.

Likewise preferred are substituted 5,6,7,8-tetrahydro-pyrido[4,3-d]-pyrimidin-2-yl and 5,6,7,8-tetrahydro-quinazolin-2-yl compounds of the above-stated general formula I, in which R⁵ denotes a linear or branched C₁₋₁₀ alkyl residue, optionally comprising one or more oxygen atoms and/or optionally one or more sulfur atoms and/or optionally one or more —N(H) groups as chain link(s), a linear or branched C₂₋₁₀ alkenyl residue, optionally comprising one or more oxygen atoms and/or optionally one or more sulfur atoms and/or optionally one or more —N(H) groups as chain link(s), a linear or branched C₂₋₁₀ alkynyl residue, optionally comprising one or more oxygen atoms and/or optionally one or more sulfur atoms and/or optionally one or more —N(H) groups as chain link(s),

an unsubstituted or at least monosubstituted, saturated or unsaturated 3- to 8-membered cycloaliphatic residue, optionally comprising one or more heteroatoms, mutually independently, selected from the group consisting of oxygen, sulfur and nitrogen as ring member(s), which residue may be attached via a —(CH₂)—, —(CH₂)₂—, —(CH₂)₃—, —(CH₂)₄—, —C(C₂H₅)(H)—, —(CH₂)—O—, —(CH₂)₂—O—, —(CH₂)₃—O—, —(CH₂)₄—O—, —O—(CH₂)—, —O—(CH₂)₂—, —O—(CH₂)₃—, —O—(CH₂)₄—, —C(C₂H₅)(H)—O—, —O—C(C₂H₅)(H)—, —CH₂—O—CH₂—, —CH₂—S—CH₂—, —C(CH₃)₂ or —C(H)(CH₃) group and/or be fused with an unsubstituted or at least monosubstituted, 5- or 6-membered monocyclic ring system,

an unsubstituted or at least monosubstituted, 5- or 6-membered aryl or heteroaryl residue, which may be attached via a —(CH₂)—, —(CH₂)₂—, —(CH₂)₃—, —(CH₂)₄—, —C(C₂H₅)(H)—, —(CH₂)—O—, —(CH₂)₂—O—, —(CH₂)₃—O—, —(CH₂)₄—O—, —O—(CH₂)—, —O—(CH₂)₂—, —O—(CH₂)₃—, —O—(CH₂)₄—, —C(C₂H₅)(H)—O—, —O—C(C₂H₅)(H)—, —CH₂—O—CH₂—, —CH₂—S—CH₂—, —C(CH₃)₂—, —C(H)(CH₃)— or —CH═CH— group and/or be fused with an unsubstituted or at least monosubstituted 5- or 6-membered, monocyclic ring system,

a —C(═O)—R⁷ residue, which may be attached via a —(CH₂)—, —(CH₂)₂ or —(CH₂)₃ group,

a —C(═O)—R⁸ residue, which may be attached via a linear or branched C₁₋₃ alkylene group which is unsubstituted or mono- or polysubstituted with a phenyl residue, or

an —N(H)—C(═O)—O—R⁹ residue, which may be attached via a linear or branched C₁₋₈ alkylene group which is unsubstituted or mono- or polysubstituted with a phenyl residue and optionally comprises at least one —N(H)—C(═O) or at least one —C(═O)—N(H) grouping as a chain link,

preferably

a residue selected from the group consisting of methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, tert-butyl, n-pentyl, neopentyl, iso-pentyl, —C(H)(C₂H₅)₂, —C(H)(n-C₃H₇)₂—, —CH═CH—CH═CH—CH₃, —CH₂—CH₂—CH═CH₂, —CH₂—CH₂—C(H)(CH₃)—(CH₂)₃—CH₃, —CH₂—O—CH₃ and —CH₂—O—CH₂—CH₂—O—CH₃,

a residue selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, piperidinyl, piperazinyl, morpholinyl, tetrahydrofuranyl (tetrahydrofuryl), dithiolanyl, 1,2,3,4-tetrahydroindolyl, 1,2,3,4-tetrahydronaphthyl, 1,3-dihydroisoindolyl, benzooxazolyl and imidazolidinyl, wherein the cyclic residue in each case may be attached via a —(CH₂)—, —(CH₂)₂—, —(CH₂)₃—, —(CH₂)₄—, —C(C₂H₅)(H)—, —(CH₂)—O—, —(CH₂)₂—O—, —(CH₂)₃—O—, —(CH₂)₄—O—, —O—(CH₂)—, —O—(CH₂)₂—, —O—(CH₂)₃—, —O—(CH₂)₄—, —C(C₂H₅)(H)—O—, —O—C(C₂H₅)(H)—, —CH₂—O—CH₂—, —CH₂—S—CH₂—, —C(CH₃)₂—, or —C(H)(CH₃) group and/or be mono- or polysubstituted, identically or differently, with a substituent selected from the group consisting of phenyl, —C(═O)—O-tert-butyl, oxo (═O), —S(═O)₂-methyl and —S(═O)₂-phenyl, wherein the above-stated phenyl residue may in each case be mono- or polysubstituted, identically or differently, with a substituent selected from the group consisting of F, Cl, Br and I,

a residue selected from the group consisting of phenyl, naphthyl, furanyl (furyl), thiophenyl (thienyl), pyridinyl, isoxazolyl, triazolyl, pyrazolyl, thiazolyl, benzo[1,2,5]-oxadiazolyl, 2,3-dihydrobenzofuranyl, quinolinyl, chromanyl, chromenyl, benzo[b]furanyl, benzo[b]thiophenyl, benzo[1,3]-dioxinyl, indolyl, 2,3-dihydro-indolyl, 3,4-dihydro-benzo[1,4]oxazinyl and 1,2,3,4-tetrahydroisoquinolinyl, wherein the cyclic residue may in each case be attached via a —(CH₂)—, —(CH₂)₂—, —(CH₂)₃—, —(CH₂)₄—, —C(C₂H₅)(H)—, —(CH₂)—O—, —(CH₂)₂—O—, —(CH₂)₃—O—, —(CH₂)₄—O—, —O—(CH₂)—, —O—(CH₂)₂—, —O—(CH₂)₃—, —O—(CH₂)₄—, —C(C₂H₅)(H)—O—, —O—C(C₂H₅)(H)—, —CH₂—O—CH₂—, —CH₂—S—CH₂—, —C(CH₃)₂—, —C(H)(CH₃) or —CH═CH— group and/or be mono- or polysubstituted, identically or differently, with a substituent selected from the group consisting of F, Cl, Br, I, —CN, —NO₂, —OH, —SH, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, n-pentyl, iso-pentyl, neopentyl, methoxy, ethoxy, n-propoxy, iso-propoxy, n-butyloxy, iso-butyloxy, sec-butyloxy, tert-butyloxy, —S-methyl, —S-ethyl, —CF₃, —CHF₂, —CH₂F, —O—CF₃, —O—CHF₂, —O—CH₂F, —S—CF₃, —S—CHF₂, —S—CH₂F, —S(═O)₂-phenyl, pyrazolyl, phenyl, —N(CH₃)₂, —N(C₂H₅)₂, —CH₂—O—C(═O)-phenyl, —O—C(═O)-phenyl, furyl (furanyl), thiadiazolyl, thiophenyl (thienyl), phenoxy and benzyl, and wherein the cyclic substituents may themselves in each case be mono- or polysubstituted, identically or differently, with a substituent selected from the group consisting of F, Cl, Br, I,

a —C(═O)—R⁷ residue, which may be attached via a —(CH₂)—, —(CH₂)₂ or —(CH₂)₃ group,

a —C(═O)—O—R⁸ residue, which may be attached via a —(CH₂)—, —(CH₂)₂—, —(CH₂)₃ or

—C(H)(phenyl) group, or

an —N(H)—C(═O)—O—R⁹ residue, which may be attached via a —(CH₂)—, —(CH₂)₂—, —(CH₂)₃—, —(CH₂)₄—, —(CH₂)₅—, —C(H)(CH₂-phenyl), —C(H)(phenyl), —C(H)(C(H)(CH₃)₂) or —C(H)(CH₂—CH(CH₃)₂)—NH—C(═O)—CH₂ group,

and the respective remaining residues X, R¹, R², R^(2a), R³, R⁴ and R⁶ to R¹¹ have the above-stated meaning, in each case optionally in the form of one of the pure stereoisomers thereof, in particular enantiomers or diastereomers, the racemates thereof or in the form of a mixture of stereoisomers, in particular the enantiomers and/or diastereomers, in any desired mixing ratio, or in each case in the form of corresponding salts, or in each case in the form of corresponding solvates.

Also preferred are substituted 5,6,7,8-tetrahydro-pyrido[4,3-d]-pyrimidin-2-yl and 5,6,7,8-tetrahydro-quinazolin-2-yl compounds of the above-stated general formula I, in which R⁶ is

a group —NR¹⁰R¹¹,

a linear or branched, unsubstituted C₁₋₁₀ alkyl residue, a linear or branched, unsubstituted C₂₋₁₀ alkenyl residue, a linear or branched, unsubstituted, C₂₋₁₀ alkynyl residue,

an unsubstituted or at least monosubstituted, saturated or unsaturated 3-, 4-, 5-, 6-, 7- or 8-membered cycloaliphatic residue, which may be attached via a linear or branched C₁₋₃ alkylene group and/or be bridged with a linear or branched C₁₋₃ alkylene group,

an unsubstituted or at least monosubstituted 5- to 6-membered aryl or heteroaryl residue, which may be attached via a linear or branched C₁₋₆ alkylene group and/or be fused with an unsubstituted or at least monosubstituted 5- or 6-membered monocyclic ring system,

preferably

a group —NR¹⁰R¹¹,

a linear or branched, unsubstituted C₁₋₅ alkyl residue, a linear or branched, unsubstituted C₂₋₅ alkenyl residue, a linear or branched, unsubstituted, C₂₋₅ alkynyl residue,

an unsubstituted or at least monosubstituted, saturated or unsaturated, 5-, 6- or 7-membered cycloaliphatic residue, which may be attached via a —(CH₂)—, —(CH₂)₂, or —(CH₂)₃ group and/or be bridged with a —(C)(CH₃)₂) group, or

an unsubstituted or at least monosubstituted, 5- or 6-membered aryl or heteroaryl residue, which may be attached via a —(CH₂)—, —(CH₂)₂—, or —(CH₂)₃ group and/or be fused with an unsubstituted or at least monosubstituted, 5- or 6-membered monocyclic ring system, optionally containing one or more oxygen atoms as ring member(s) and/or one or more nitrogen atoms as ring member(s),

particularly preferably

a group —NR¹⁰R¹¹,

a methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl or tert-butyl residue,

a 7,7-dimethyl-2-oxo-bicyclo[2.2.1]heptyl residue optionally attached via a —(CH₂)—, —(CH₂)₂ or —(CH₂)₃ group, or

a phenyl, naphthyl, thiophenyl (thienyl), furanyl, (furyl), thiazolyl, pyrazolyl, 2,3-dihydro-benzo[1,4]-dioxinyl, 1,2,3,4-tetrahydroiso-quinolinyl or 3,4-dihydrobenzo[1,4]oxazinyl residue, which may be attached via a —(CH₂), —(CH₂)₂, or —(CH₂)₃ group and/or be mono- or polysubstituted, identically or differently, with a substituent selected from the group consisting of F, Cl, Br, I, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, n-pentyl, iso-pentyl, neopentyl, methoxy, ethoxy, —CN, —CF₃, —CF₂H, —CFH₂, —NO₂, —C(═O)—CF₃, —O—CF₃, —C(═O)—O—CH₃, —C(═O)—O—C₂H₅, —NH—C(═O)—CH₃, —S(═O)₂—CH₃ and phenyl,

and the respective remaining residues X, R¹, R², R^(2a), R³, R⁵ and R⁷ to R¹¹ have the above-stated meaning, in each case optionally in the form of one of the pure stereoisomers thereof, in particular enantiomers or diastereomers, the racemates thereof or in the form of a mixture of stereoisomers, in particular the enantiomers and/or diastereomers, in any desired mixing ratio, or in each case in the form of corresponding salts, or in each case in the form of corresponding solvates.

Moreover, those substituted 5,6,7,8-tetrahydro-pyrido[4,3-d]-pyrimidin-2-yl and 5,6,7,8-tetrahydro-quinazolin-2-yl compounds of the above-stated general formula I are preferred, in which the residue R⁷ denotes a linear or branched, unsubstituted C₁₋₃ alkyl residue, an unsubstituted, 5- or 6-membered aryl or heteroaryl residue, an unsubstituted, saturated or unsaturated 5-, 6- or 7-membered cycloaliphatic residue, optionally comprising a nitrogen atom as a ring member, which residue may be fused with an unsubstituted, 6-membered monocyclic ring system, or an —NR^(7a)R^(7b) residue, in which the residues R^(7a) and R^(7b), identical or different, in each case denote a linear or branched C₁₋₃ alkyl residue,

preferably a methyl, ethyl, n-propyl, phenyl, indolyl, 2,3-dihydroindolyl, dimethylamino or diethylamino residue,

and the respective remaining residues X, R¹, R², R^(2a), R³ to R⁶ and R⁸ to R¹¹ have the above-stated meaning, in each case optionally in the form of one of the pure stereoisomers thereof, in particular enantiomers or diastereomers, the racemates thereof or in the form of a mixture of stereoisomers, in particular the enantiomers and/or diastereomers, in any desired mixing ratio, or in each case in the form of corresponding salts, or in each case in the form of corresponding solvates.

Likewise preferred are substituted 5,6,7,8-tetrahydro-pyrido[4,3-d]-pyrimidin-2-yl and 5,6,7,8-tetrahydro-quinazolin-2-yl compounds of the above-stated general formula I, in which R⁸ denotes a linear or branched, unsubstituted C₁₋₃ alkyl residue or a phenyl residue optionally attached via a linear or branched C₁₋₃ alkylene group,

particularly preferably a methyl, ethyl, phenyl or benzyl residue,

and the respective remaining residues X, R¹, R², R^(2a), R³ to R⁷ and R⁹ to R¹¹ have the above-stated meaning, in each case optionally in the form of one of the pure stereoisomers thereof, in particular enantiomers or diastereomers, the racemates thereof or in the form of a mixture of stereoisomers, in particular the enantiomers and/or diastereomers, in any desired mixing ratio, or in each case in the form of corresponding salts, or in each case in the form of corresponding solvates.

Also preferred are substituted 5,6,7,8-tetrahydro-pyrido[4,3-d]-pyrimidin-2-yl and 5,6,7,8-tetrahydro-quinazolin-2-yl compounds of the above-stated general formula I, in which R⁹ denotes a linear or branched, unsubstituted C₁₋₃ alkyl residue, an unsubstituted 5- or 6-membered aryl or heteroaryl residue, optionally attached via a linear or branched C₁₋₃ alkylene group, or an unsubstituted or at least monosubstituted, saturated or unsaturated, 5- or 6-membered cycloaliphatic residue, which may be fused with at least one unsubstituted, 6-membered monocyclic ring system,

preferably a methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, or a phenyl or fluorenyl residue optionally attached via a —(CH₂) group,

and the respective remaining residues X, R¹, R², R^(2a), R³ to R⁸ and R¹⁰ and R¹¹ have the above-stated meaning, in each case optionally in the form of one of the pure stereoisomers thereof, in particular enantiomers or diastereomers, the racemates thereof or in the form of a mixture of stereoisomers, in particular the enantiomers and/or diastereomers, in any desired mixing ratio, or in each case in the form of corresponding salts, or in each case in the form of corresponding solvates.

Likewise preferred are substituted 5,6,7,8-tetrahydro-pyrido[4,3-d]-pyrimidin-2-yl and 5,6,7,8-tetrahydro-quinazolin-2-yl compounds of the above-stated general formula I, in which the residues R¹⁰ and R¹¹, identical or different, in each case denote a methyl, ethyl, n-propyl or iso-propyl residue, and the respective remaining residues X, R¹, R², R^(2a) and R³ to R⁹ have the above-stated meaning, in each case optionally in the form of one of the pure stereoisomers thereof, in particular enantiomers or diastereomers, the racemates thereof or in the form of a mixture of stereoisomers, in particular the enantiomers and/or diastereomers, in any desired mixing ratio, or in each case in the form of corresponding salts, or in each case in the form of corresponding solvates.

Particularly preferred are substituted 5,6,7,8-tetrahydro-pyrido[4,3-d]-pyrimidin-2-yl and 5,6,7,8-tetrahydro-quinazolin-2-yl compounds of the general formula I,

in which

X denotes a C(H)(NHR²) group or an NR^(2a) group,

R¹ denotes a —C(═O)—R³ group or a —C(═O)—O—R⁴ group,

R², R^(2a), mutually independently, in each case denote a —C(═O)—R⁵ group or an —S(═O)₂—R⁶ group,

R³ denotes a methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl or tert-butyl residue, an unsubstituted, saturated or unsaturated 5-, 6- or 7-membered cycloaliphatic residue, optionally comprising one or more oxygen atoms and/or one or more nitrogen atoms as ring member(s), which residue may be attached via a —(CH₂), —(CH₂)₂ or —(CH₂)₃ group, or a phenyl residue, thiophenyl residue (thienyl residue), furanyl residue (furyl residue), pyridinyl residue or naphthyl residue, which may be attached via a —(CH₂), —(CH₂)₂ or —(CH₂)₃ group and/or be mono- or polysubstituted, identically or differently, with a substituent selected from the group consisting of methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, methoxy, ethoxy, n-propoxy, iso-propoxy, n-butoxy, iso-butoxy, sec-butoxy, tert-butoxy, F, Cl, Br, I, —CN and —CF₃,

R⁴ denotes an unsubstituted benzyl residue,

R⁵ denotes a residue selected from the group consisting of methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, tert-butyl, n-pentyl, iso-pentyl, neopentyl, —C(H)(C₂H₅)₂, —C(H)(n-C₃H₇)₂, —CH═CH—CH═CH—CH₃, —CH₂—CH₂—CH═CH₂, —CH₂—CH₂—C(H)(CH₃)—(CH₂)₃—CH₃, —CH₂—O—CH₃ and —CH₂—O—CH₂—CH₂—O—CH₃,

a residue selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, piperidinyl, piperazinyl, morpholinyl, tetrahydrofuranyl (tetrahydrofuryl), dithiolanyl, 1,2,3,4-tetrahydroindolyl, 1,2,3,4-tetrahydronaphthyl, 1,3-dihydroisoindolyl, benzooxazolyl and imidazolidinyl, wherein the cyclic residue may in each case be attached via a —(CH₂), —(CH₂)₂, —(CH₂)₃, —(CH₂)₄, —C(C₂H₅)(H), —(CH₂)—O, —(CH₂)₂—O, —(CH₂)₃—O, —(CH₂)₄—O, —O—(CH₂), —O—(CH₂)₂, —O—(CH₂)₃, —O—(CH₂)₄, —C(C₂H₅)(H)—O, —O—C(C₂H₅)(H), —CH₂—O—CH₂, —CH₂—S—CH₂, —C(CH₃)₂, or —C(H)(CH₃) group and/or be mono- or polysubstituted, identically or differently, with a substituent selected from the group consisting of phenyl, —C(═O)—O-tert-butyl, oxo (═O), —S(═O)₂-methyl and —S(═O)₂-phenyl, and wherein the above-stated phenyl residues may in each case be mono- or polysubstituted, identically or differently, with a substituent selected from the group consisting of F, Cl, Br and I,

a residue selected from the group consisting of phenyl, naphthyl, furanyl (furyl), thiophenyl (thienyl), pyridinyl, isoxazolyl, triazolyl, pyrazolyl, thiazolyl, benzo[1,2,5]-oxadiazolyl, 2,3-dihydrobenzofuranyl, quinolinyl, chromanyl, chromenyl, benzo[b]furanyl, benzo[b]thiophenyl, benzo[1,3]-dioxinyl, indolyl, 2,3-dihydro-indolyl, 3,4-dihydro-benzo[1,4]oxazinyl and 1,2,3,4-tetrahydroisoquinolinyl, wherein the cyclic residue may in each case be attached via a —(CH₂), —(CH₂)₂, —(CH₂)₃, —(CH₂)₄, —C(C₂H₅)(H), —(CH₂)—O, —(CH₂)₂—O, —(CH₂)₃—O, —(CH₂)₄—O, —O—(CH₂)—, —O—(CH₂)₂—, —O—(CH₂)₃, —O—(CH₂)₄, —C(C₂H₅)(H)—O, —O—C(C₂H₅)(H), —CH₂—O—CH₂, —CH₂—S—CH₂, —C(CH₃)₂, —C(H)(CH₃) or —CH═CH— group and/or be mono- or polysubstituted, identically or differently, with a substituent selected from the group consisting of F, Cl, Br, I, —CN, —NO₂, —OH, —SH, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, n-pentyl, neopentyl, methoxy, ethoxy, n-propoxy, iso-propoxy, n-butyloxy, iso-butyloxy, sec-butyloxy, tert-butyloxy, —S-methyl, —S-ethyl, —CF₃, —CHF₂, —CH₂F, —O—CF₃, —O—CHF₂, —O—CH₂F, —S—CF₃, —S—CHF₂, —S—CH₂F, —S(═O)₂-phenyl, pyrazolyl, phenyl, —N(CH₃)₂, —N(C₂H₅)₂, —CH₂—O—C(═O)-phenyl, —O—C(═O)-phenyl, furyl (furanyl), thiadiazolyl, thiophenyl (thienyl), phenoxy and benzyl, and wherein the cyclic substituents may themselves in each case be mono- or polysubstituted, identically or differently, with a substituent selected from the group consisting of F, Cl, Br, I,

denotes a —C(═O)—R⁷ residue, which may be attached via a —(CH₂)—, —(CH₂)₂ or —(CH₂)₃ group,

a —C(═O)—O—R⁸ residue, which may be attached via a —(CH₂), —(CH₂)₂, —(CH₂)₃ or —C(H)(phenyl) group, or

an —N(H)—C(═O)—O—R⁹ residue, which may be attached via a —(CH₂), —(CH₂)₂, —(CH₂)₃, —(CH₂)₄, —(CH₂)₅, —C(H)(CH₂-phenyl), —C(H)(phenyl), —C(H)(C(H)(CH₃)₂) or —C(H)(CH₂—CH(CH₃)₂)—NH—C(═O)—CH₂ group,

R⁶ denotes a group —NR¹⁰R¹¹,

a methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl or tert-butyl residue,

a 7,7-dimethyl-2-oxo-bicyclo[2.2.1]heptyl residue optionally attached via a —(CH₂)—, —(CH₂)₂ or —(CH₂)₃ group, or

a phenyl, naphthyl, thiophenyl (thienyl), furanyl, (furyl), thiazolyl, pyrazolyl, 2,3-dihydro-benzo[1,4]-dioxinyl, 1,2,3,4-tetrahydroiso-quinolinyl or 3,4-dihydrobenzo[1,4]oxazinyl residue, which may be attached via a —(CH₂), —(CH₂)₂, or —(CH₂)₃ group and/or be mono- or polysubstituted, identically or differently, with a substituent selected from the group consisting of F, Cl, Br, I, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, n-pentyl, iso-pentyl, neopentyl, methoxy, ethoxy, —CN, —CF₃, —CF₂H, —CFH₂, —NO₂, —C(═O)—CF₃, —O—CF₃, —C(═O)—O—CH₃, —C(═O)—O—C₂H₅, —NH—C(═O)—CH₃, —S(═O)₂—CH₃ and phenyl,

R⁷ denotes a methyl, ethyl, n-propyl, phenyl, indolyl, 2,3-dihydroindolyl, dimethylamino or diethylamino residue

R⁸ denotes a methyl, ethyl, phenyl or benzyl residue,

R⁹ denotes a methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, or a phenyl or fluorenyl residue optionally attached via a —(CH₂) group,

R¹⁰, R¹¹, identical or different, in each case denote a methyl, ethyl, n-propyl or iso-propyl residue,

in each case optionally in the form of one of the pure stereoisomers thereof, in particular enantiomers or diastereomers, the racemates thereof or in the form of a mixture of stereoisomers, in particular the enantiomers and/or diastereomers, in any desired mixing ratio, or in each case in the form of corresponding salts or in each case in the form of corresponding solvates.

Very particularly preferred are substituted 5,6,7,8-tetrahydropyrido-[4,3-d]pyrimidin-2-yl and 5,6,7,8-tetrahydro-quinazolin-2-yl compounds of the general formula I selected from the group consisting of

-   [1]     3-fluoro-N-[6-(4-fluoro-benzoyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-benzamide, -   [2]     3,5-dichloro-N-[6-(3-fluoro-4-methoxy-benzoyl)-5,6,7,8-tetrahydro-pyrido-[4,3-d]pyrimidin-2-yl]-benzamide, -   [3]     4-tert-butyl-N-(6-hexanoyl-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl)-benzamide, -   [4]     N-(6-acetyl-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl)-3,4-dichloro-benzamide, -   [5]     3,5-dichloro-N-[6-(3-trifluoromethyl-benzoyl)-5,6,7,8-tetrahydro-pyrido-[4,3-d]pyrimidin-2-yl]-benzamide, -   [6]     3-chloro-N-[6-(4-methoxy-2,3,6-trimethyl-benzenesulfonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-benzamide, -   [7]     N-[6-(2-ethoxy-benzoyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-3-fluoro-benzamide, -   [8]     3-chloro-N-[6-(3-phenyl-propionyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]-pyrimidin-2-yl]-benzamide, -   [9]     4-tert-butyl-N-[6-(isoxazole-5-carbonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]-pyrimidin-2-yl]-benzamide, -   [10]     N-[6-(2-benzylsulfanyl-acetyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-2-methoxy-benzamide, -   [11] thiophene-2-carboxylic acid     {6-[2-(4-chloro-phenyl)-2-methyl-propionyl]-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl}-amide, -   [12]     N-(6-benzoyl-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl)-3-methyl-benzamide, -   [13]     N-[6-(2,3-dihydro-benzofuran-5-carbonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]-pyrimidin-2-yl]-2-fluoro-benzamide, -   [14] thiophene-2-carboxylic acid     [6-(3,4,5-trimethoxy-benzoylamino)-5,6,7,8-tetrahydro-quinazolin-2-yl]-amide, -   [15] naphthalene-1-carboxylic acid     [6-(3-methyl-5-phenyl-isoxazole-4-carbonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-amide, -   [16]     3-chloro-N-{6-[2-(5-methyl-2-phenyl-thiazol-4-yl)-acetyl]-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl}-benzamide, -   [17]     N-[6-(4-chloro-2,5-dimethyl-benzenesulfonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-2-trifluoromethyl-benzamide, -   [18]     N-[6-(1-benzenesulfonyl-1H-indole-2-carbonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-3-methoxy-benzamide, -   [20]     N-[6-(5-methyl-1-phenyl-1H-pyrazole-4-sulfonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-2-trifluoromethyl-benzamide, -   [21]     N-[6-(3-chloro-2-methyl-benzenesulfonyl)-5,6,7,8-tetrahydro-pyrido[4,3-(d)]pyrimidin-2-yl]-3-fluoro-benzamide, -   [22]     3,5-dichloro-N-[6-(3,5-dimethyl-isoxazole-4-carbonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-benzamide, -   [23] thiophene-2-carboxylic acid     [6-(4-trifluoromethoxy-benzenesulfonylamino)-5,6,7,8-tetrahydro-quinazolin-2-yl]-amide, -   [25]     N-[6-(furan-2-carbonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-3-methoxy-benzamide, -   [26]     N-{6-[4-(2,3-dihydro-indol-1-yl)-4-oxo-butyryl]-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl}-3-methyl-benzamide, -   [27]     N-{6-[2-(4-methyl-cyclohexyl)-acetyl]-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl}-2-trifluoromethyl-benzamide, -   [28]     3,4-difluoro-N-[6-(6-phenoxy-pyridine-3-carbonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-benzamide, -   [29]     4-tert-butyl-N-[6-(2-phenyl-thiazole-4-carbonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-benzamide, -   [30]     3,5-dichloro-N-[6-(2-trifluoromethyl-benzenesulfonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-benzamide, -   [31] thiophene-2-carboxylic acid     [6-(3-bromo-benzenesulfonylamino)-5,6,7,8-tetrahydro-quinazolin-2-yl]-amide, -   [32]     N-[6-(2-chloro-pyridine-4-carbonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-3-methoxy-benzamide, -   [33]     4-fluoro-N-[6-(2-methanesulfonyl-benzenesulfonylamino)-5,6,7,8-tetrahydro-quinazolin-2-yl]-benzamide, -   [35]     N-(6-dimethylsulfamoyl-5,6,7,8-tetrahydro-pyrido[4,3-(d)]pyrimidin-2-yl)-3-fluoro-benzamide, -   [36]     3-fluoro-N-{6-[2-(4-trifluoromethyl-phenyl)-acetyl]-5,6,7,8-tetrahydro-pyrido[4,3-(d)]pyrimidin-2-yl}-benzamide, -   [37]     N-{6-[2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-acetyl]-5,6,7,8-tetrahydro-pyrido[4,3-(d)]pyrimidin-2-yl}-2-trifluoromethyl-benzamide, -   [38] thiophene-2-carboxylic acid     {6-[4-(4-chloro-2-methyl-phenoxy)-butyrylamino]-5,6,7,8-tetrahydro-quinazolin-2-yl}-amide, -   [39]     N-[6-(butane-1-sulfonyl)-5,6,7,8-tetrahydro-pyrido[4,3-(d)]pyrimidin-2-yl]-3-fluoro-benzamide, -   [40]     2-methoxy-N-[6-(2-propyl-pentanoyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-benzamide, -   [41]     N-[6-(4,5-dichloro-thiophene-2-sulfonylamino)-5,6,7,8-tetrahydro-quinazolin-2-yl]-4-fluoro-benzamide, -   [42]     4-chloro-N-[6-(2-trifluoromethyl-benzenesulfonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-benzamide, -   [43] thiophene-2-carboxylic acid     [6-(4-methoxy-benzenesulfonylamino)-5,6,7,8-tetrahydro-quinazolin-2-yl]-amide, -   [44]     5-[2-(3,4-difluoro-benzoylamino)-7,8-dihydro-5H-pyrido[4,3-(d)]pyrimidin-6-yl]-5-oxo-valeric     acid methyl ester, -   [45]     N-[6-(benzo[b]thiophene-3-carbonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-4-chloro-benzamide, -   [46]     N-[6-(5-bromo-2-methoxy-benzenesulfonylamino)-5,6,7,8-tetrahydro-quinazolin-2-yl]-4-fluoro-benzamide, -   [47]     4-fluoro-N-[6-(4-fluoro-benzenesulfonylamino)-5,6,7,8-tetrahydro-quinazolin-2-yl]-benzamide, -   [48]     N-{6-[2-(1H-indol-3-yl)-2-oxo-acetyl]-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl}-2-trifluoromethyl-benzamide, -   [49] 5-tert-butyl-2-methyl-furan-3-carboxylic acid     {2-[(thiophene-2-carbonyl)-amino]-5,6,7,8-tetrahydro-quinazolin-6-yl}-amide, -   [50]     N-[6-(2,5-dimethoxy-benzenesulfonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-3-methoxy-benzamide, -   [51] benzoic acid     2-{2-[(thiophene-2-carbonyl)-amino]-5,6,7,8-tetrahydro-quinazolin-6-ylcarbamoyl}-benzyl     ester, -   [52]     3,4-difluoro-N-(6-hexanoyl-5,6,7,8-tetrahydro-pyrido[4,3-(d)]pyrimidin-2-yl)-benzamide, -   [53]     4-ethyl-N-[6-(tetrahydro-furan-2-carbonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-benzamide, -   [54]     N-[6-(2-chloro-benzenesulfonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-3-fluoro-benzamide, -   [55]     4-tert-butyl-N-[6-(5-tert-butyl-2-methyl-2H-pyrazole-3-carbonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-benzamide, -   [56]     3-methoxy-N-[6-(4-methoxy-benzenesulfonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-benzamide, -   [57]     {2-[2-(3,4-difluoro-benzoylamino)-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-6-yl]-2-oxo-1-phenyl-ethyl}-carbamic     acid benzyl ester, -   [58] 5-phenyl-oxazole-4-carboxylic acid     {2-[(thiophene-2-carbonyl)-amino]-5,6,7,8-tetrahydro-quinazolin-6-yl}-amide, -   [59]     4-chloro-N-(6-dimethylsulfamoyl-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl)-benzamide, -   [60]     4-tert-butyl-N-[6-(2-fluoro-benzenesulfonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-benzamide, -   [61]     4-chloro-N-[6-(3-cyclopentyl-propionyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-benzamide, -   [62]     4-chloro-N-[6-(4-phenyl-butyryl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-benzamide, -   [63]     4-tert-butyl-N-[6-(5-methyl-2-phenyl-2H-[1,2,3]triazole-4-carbonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-benzamide, -   [64]     2-chloro-N-{2-[(thiophene-2-carbonyl)-amino]-5,6,7,8-tetrahydro-quinazolin-6-yl}-isonicotinamide, -   [66]     N-[6-(5-chloro-thiophene-2-sulfonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-3-fluoro-benzamide, -   [67]     N-[6-(4-diethylamino-benzoyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-3-methoxy-benzamide, -   [68]     N-[6-(2,4-dimethyl-thiazole-5-sulfonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-3-methyl-benzamide, -   [69]     4-chloro-N-[6-naphthalene-2-carbonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-benzamide, -   [70]     N-[6-(2,4-difluoro-benzenesulfonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-2-methoxy-benzamide, -   [71]     3,4-dichloro-N-[6-(4-chloro-benzenesulfonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-benzamide, -   [72]     3,4-difluoro-N-[6-(thiophene-2-sulfonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-benzamide, -   [74]     4-ethyl-N-[6-(4-pyrazol-1-yl-benzoyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-benzamide, -   [75]     N-[6-(7,7-dimethyl-2-oxo-bicyclo[2.2.1]hept-1-ylmethanesulfonylamino)-5,6,7,8-tetrahydro-quinazolin-2-yl]-butyramide, -   [76] 5-oxo-5-phenyl-valeric acid     (2-butyrylamino-5,6,7,8-tetrahydro-quinazolin-6-yl)-amide, -   [77]     3-[2-(4-chloro-benzoylamino)-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-6-yl]-3-oxo-propionic     acid methyl ester, -   [78]     N-{6-[5-(4-chloro-phenyl)-2-methyl-furan-3-carbonyl]-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl}-2-methoxy-benzamide, -   [79]     4-chloro-N-[6-(2,4-dimethyl-thiazole-5-sulfonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-benzamide, -   [80]     N-[6-(2,3-difluoro-benzoyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-3-methoxy-benzamide, -   [81]     4-chloro-N-{6-[2-(2-methoxy-ethoxy)-acetyl]-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl}-benzamide, -   [82]     2-[2-(2-ethoxy-benzoylamino)-7,8-dihydro-5H-pyrido[4,3-d]pyrimidine-6-sulfonyl]-benzoic     acid methyl ester, -   [83]     4-tert-butyl-N-[6-(4-nitro-benzenesulfonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-benzamide, -   [86]     N-[6-(5-chloro-thiophene-2-sulfonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-2-methoxy-benzamide, -   [87]     4-fluoro-N-[6-(furan-2-carbonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-benzamide, -   [88]     4-{2-[(thiophene-2-carbonyl)-amino]-5,6,7,8-tetrahydro-quinazolin-6-ylcarbamoyl}-piperidine-1-carboxylic     acid tert-butyl ester, -   [89] 1-(4-chloro-phenyl)-cyclopropanecarboxylic acid     (2-butyrylamino-5,6,7,8-tetrahydro-quinazolin-6-yl)-amide, -   [90]     N-(6-ethanesulfonyl-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl)-3-methoxy-benzamide, -   [91] 5-methyl-thiophene-2-carboxylic acid     (2-butyrylamino-5,6,7,8-tetrahydro-quinazolin-6-yl)-amide, -   [92]     4-tert-butyl-N-[6-(4-methyl-3-nitro-benzoyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-benzamide, -   [94]     4-fluoro-N-[6-(3-phenyl-propionylamino)-5,6,7,8-tetrahydro-quinazolin-2-yl]-benzamide, -   [95]     3,4-dichloro-N-[6-(2,4,6-trimethyl-benzenesulfonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-benzamide, -   [96]     N-[6-(4-methyl-3,4-dihydro-2H-benzo[1,4]oxazine-7-sulfonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-nicotinamide, -   [97] thiophene-2-carboxylic acid     [6-(3,5-difluoro-benzoylamino)-5,6,7,8-tetrahydro-quinazolin-2-yl]-amide, -   [98]     N-[6-(2,4-difluoro-benzenesulfonylamino)-5,6,7,8-tetrahydro-quinazolin-2-yl]-butyramide, -   [99] thiophene-2-carboxylic acid     [6-(2,3,5,6-tetramethyl-benzenesulfonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-amide, -   [101]     N-[6-(3,4-dichloro-benzoyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-4-ethyl-benzamide, -   [102]     N-[6-(7,7-dimethyl-2-oxo-bicyclo[2.2.1]hept-1-ylmethanesulfonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-3-fluoro-benzamide, -   [103]     N-[6-(6-fluoro-4H-benzo[1,3]dioxin-8-carbonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-2-trifluoromethyl-benzamide, -   [104]     [5-(2-butyrylamino-5,6,7,8-tetrahydro-quinazolin-6-ylcarbamoyl)-pentyl]-carbamic     acid benzyl ester, -   [105]     2-ethoxy-N-[6-(4-oxo-pentanoyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-benzamide, -   [106] naphthalene-1-carboxylic acid     [6-(propane-1-sulfonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-amide, -   [107]     N-[6-(5-fluoro-2-methyl-benzenesulfonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-4-methyl-benzamide, -   [109]     3-chloro-N-[6-(2-methyl-benzoyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-benzamide, -   [110] thiophene-2-carboxylic acid     [6-(3-chloro-benzo[b]thiophene-2-carbonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-amide, -   [112] thiophene-2-carboxylic acid     [6-(2-cyclopentyl-acetylamino)-5,6,7,8-tetrahydro-quinazolin-2-yl]-amide, -   [113]     N-[6-(3,4-dichloro-benzoyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-2-fluoro-benzamide, -   [114]     N-[6-(2-chloro-benzenesulfonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-4-ethyl-benzamide, -   [115] thiophene-2-carboxylic acid     [6-(4-bromo-3-methyl-benzoylamino)-5,6,7,8-tetrahydro-quinazolin-2-yl]-amide, -   [116]     3-methyl-N-[6-(toluene-3-sulfonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-benzamide, -   [117] naphthalene-1-carboxylic acid     [6-(5-chloro-thiophene-2-sulfonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-amide, -   [118]     N-(2-butyrylamino-5,6,7,8-tetrahydro-quinazolin-6-yl)-2,6-difluoro-benzamide, -   [119]     3-chloro-N-[6-(3,4-dimethoxy-benzoyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-benzamide, -   [120]     N-[6-(3-chloro-benzo[b]thiophene-2-carbonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-benzamide, -   [121]     4-ethyl-N-[6-(thiophene-3-sulfonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-benzamide, -   [123]     2-ethoxy-N-[6-(2-ethylsulfanyl-pyridine-3-carbonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-benzamide, -   [124]     3-[2-(3-chloro-benzoylamino)-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-6-yl]-3-oxo-propionic     acid ethyl ester, -   [125]     N-[6-(3-bromo-benzenesulfonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-3-chloro-benzamide, -   [126]     3,4-dichloro-N-{6-[2-(4-chloro-phenyl)-acetyl]-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl}-benzamide, -   [127]     3-chloro-N-[6-(2-chloro-6-fluoro-benzoyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-benzamide, -   [128]     4-fluoro-N-(6-hexanoylamino-5,6,7,8-tetrahydro-quinazolin-2-yl)-benzamide, -   [129]     N-[6-(5-bromo-2-methoxy-benzenesulfonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-3-methoxy-benzamide, -   [132]     N-[6-(3-cyclopentyl-propionyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-isonicotinamide, -   [133] 5-benzyl-furan-2-carboxylic acid     (2-butyrylamino-5,6,7,8-tetrahydro-quinazolin-6-yl)-amide -   [134]     3,4-dichloro-N-[6-(4-trifluoromethoxy-benzenesulfonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-benzamide, -   [135]     [(2-butyrylamino-5,6,7,8-tetrahydro-quinazolin-6-ylcarbamoyl)-phenyl-methyl]-carbamic     acid benzyl ester, -   [136]     N-[6-(3,4-dimethoxy-benzenesulfonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-4-fluoro-benzamide, -   [137]     2-fluoro-N-[6-(2-methyl-5-phenyl-furan-3-carbonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-benzamide, -   [138] thiophene-2-carboxylic acid     (6-pent-4-enoylamino-5,6,7,8-tetrahydro-quinazolin-2-yl)-amide, -   [139]     (2-methyl-1-{2-[(thiophene-2-carbonyl)-amino]-5,6,7,8-tetrahydro-quinazolin-6-ylcarbamoyl}-propyl)-carbamic     acid 9H-fluoren-9-ylmethyl ester, -   [140]     (5-{2-[(thiophene-2-carbonyl)-amino]-5,6,7,8-tetrahydro-quinazolin-6-ylcarbamoyl}-pentyl)-carbamic     acid tert-butyl ester, -   [141]     3-fluoro-N-[6-(1,2,3,4-tetrahydro-naphthalene-2-carbonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-benzamide, -   [142]     4-chloro-N-{6-[2-(2,5-dioxo-imidazolidin-4-yl)-acetyl]-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl}-benzamide, -   [143]     3-fluoro-N-[6-(toluene-4-sulfonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-benzamide, -   [144]     3,5-dichloro-N-[6-(4-thiophen-2-yl-benzoyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-benzamide, -   [145]     N-[6-(3-chloro-thiophene-2-carbonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-2-ethoxy-benzamide, -   [146]     N-[6-(toluene-3-sulfonylamino)-5,6,7,8-tetrahydro-quinazolin-2-yl]-butyramide, -   [147] thiophene-2-carboxylic acid     {6-[2-(2,2,2-trifluoro-acetyl)-1,2,3,4-tetrahydro-isoquinoline-7-sulfonylamino]-5,6,7,8-tetrahydro-quinazolin-2-yl}-amide, -   [148]     4-methyl-N-[6-(4-trifluoromethylsulfanyl-benzoyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-benzamide, -   [149]     (2-{2-[(thiophene-2-carbonyl)-amino]-5,6,7,8-tetrahydro-quinazolin-6-ylcarbamoyl}-ethyl)-carbamic     acid tert-butyl ester, -   [150]     2-fluoro-N-[6-(2-methyl-5-nitro-benzenesulfonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-benzamide, -   [151]     N-[6-(4-methoxy-benzenesulfonylamino)-5,6,7,8-tetrahydro-quinazolin-2-yl]-butyramide, -   [152]     4-chloro-N-[6-(2,4-difluoro-benzoyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-benzamide -   [153]     4-methyl-N-(6-pent-4-enoyl-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl)-benzamide, -   [154] naphthalene-1-carboxylic acid     [6-(3-fluoro-4-methyl-benzoyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-amide, -   [155]     N-{6-[2-(4-trifluoromethyl-phenyl)-acetyl]-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl}-benzamide, -   [156]     N-[6-(3,4-dichloro-benzoyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-nicotinamide, -   [157]     4-ethyl-N-{6-[2-(2,2,2-trifluoro-acetyl)-1,2,3,4-tetrahydro-isoquinoline-7-sulfonyl]-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl}-benzamide, -   [158]     2-methoxy-N-[6-(4-methoxy-2,3,6-trimethyl-benzenesulfonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-benzamide, -   [159]     4-ethyl-N-[6-(2-methoxy-acetyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-benzamide, -   [160]     4-fluoro-N-[6-(propane-1-sulfonylamino)-5,6,7,8-tetrahydro-quinazolin-2-yl]-benzamide, -   [162]     N-[6-(7,7-dimethyl-2-oxo-bicyclo[2.2.1]hept-1-ylmethanesulfonylamino)-5,6,7,8-tetrahydro-quinazolin-2-yl]-butyramide, -   [163]     N-{6-[2-(2,5-dimethyl-phenyl)-acetylamino]-5,6,7,8-tetrahydro-quinazolin-2-yl}-4-fluoro-benzamide, -   [165] thiophene-2-carboxylic acid     (6-phenylmethanesulfonylamino-5,6,7,8-tetrahydro-quinazolin-2-yl)-amide, -   [166]     N-[6-(3,4-dimethoxy-benzenesulfonylamino)-5,6,7,8-tetrahydro-quinazolin-2-yl]-butyramide, -   [167]     N-{6-[4-(1,1-dimethyl-propyl)-benzenesulfonylamino]-5,6,7,8-tetrahydro-quinazolin-2-yl}-butyramide, -   [168]     N-(2-butyrylamino-5,6,7,8-tetrahydro-quinazolin-6-yl)-3-(3-trifluoromethyl-phenyl)-acrylamide, -   [169]     N-[6-(butane-1-sulfonylamino)-5,6,7,8-tetrahydro-quinazolin-2-yl]-4-fluoro-benzamide, -   [170] naphthalene-1-carboxylic acid     (6-acetyl-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl)-amide, -   [171]     3,5-dichloro-N-[6-(3-diethylcarbamoyl-propionyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-benzamide, -   [172]     4-ethyl-N-[6-(4-methoxy-benzenesulfonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-benzamide, -   [173]     4-ethyl-N-[6-(quinoline-6-carbonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-benzamide, -   [174]     N-[6-(2-cyclopropyl-acetyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-2-fluoro-benzamide, -   [175]     N-[6-(2H-chromene-3-carbonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-3,4-difluoro-benzamide, -   [176]     N-{6-[2-(4-chloro-phenyl)-propionyl]-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl}-benzamide, -   [177] thiophene-2-carboxylic acid     [6-(2-naphthalen-1-yl-acetylamino)-5,6,7,8-tetrahydro-quinazolin-2-yl]-amide, -   [178]     4-fluoro-N-(6-phenylmethanesulfonyl-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl)-benzamide, -   [180] thiophene-2-carboxylic acid     [6-(2,5-dichloro-thiophene-3-sulfonylamino)-5,6,7,8-tetrahydro-quinazolin-2-yl]-amide, -   [181]     {5-[2-(4-fluoro-benzoylamino)-5,6,7,8-tetrahydro-quinazolin-6-ylcarbamoyl]-pentyl}-carbamic     acid benzyl ester, -   [182]     N-[6-(2,5-dimethyl-2H-pyrazole-3-carbonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-4-ethyl-benzamide, -   [183] naphthalene-1-carboxylic acid     [6-(3-fluoro-benzoyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-amide, -   [184]     N-[6-(benzo[b]thiophene-3-carbonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-4-tert-butyl-benzamide, -   [185]     4-fluoro-N-[6-(4-methoxy-benzenesulfonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-benzamide, -   [186]     4-tert-butyl-N-[6-(2,3-dihydro-benzo[1,4]dioxin-6-sulfonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-benzamide, -   [187]     3-chloro-N-{6-[2-(2,6-dichloro-phenyl)-acetyl]-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl}-benzamide, -   [188] thiophene-2-carboxylic acid     [6-(2,3-dihydro-benzo[1,4]dioxin-6-sulfonylamino)-5,6,7,8-tetrahydro-quinazolin-2-yl]-amide, -   [189]     N-{6-[2-(3-chloro-phenoxy)-acetyl]-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl}-4-methyl-benzamide, -   [190]     N-[6-(5-phenyl-pentanoyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-benzamide, -   [191]     4-ethyl-N-[6-(2-ethyl-butyryl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-benzamide, -   [192]     3,5-dichloro-N-[6-(4-trifluoromethoxy-benzoyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-benzamide, -   [193] naphthalene-1-carboxylic acid     [6-(4-methyl-octanoyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-amide, -   [194]     4-[2-(4-fluoro-benzoylamino)-5,6,7,8-tetrahydro-quinazolin-6-ylcarbamoyl]-piperidine-1-carboxylic     acid tert-butyl ester, -   [195]     N-[6-(2-benzyloxy-acetyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-2-methoxy-benzamide, -   [196]     N-[6-(2-trifluoromethyl-benzenesulfonylamino)-5,6,7,8-tetrahydro-quinazolin-2-yl]-butyramide, -   [197]     N-[2-(4-fluoro-benzoylamino)-5,6,7,8-tetrahydro-quinazolin-6-yl]-2-methyl-6-trifluoromethyl-nicotinamide, -   [198]     N-[6-(3-cyano-benzoyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-2-trifluoromethyl-benzamide, -   [199]     3-methoxy-N-[6-(3-trifluoromethoxy-benzoyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-benzamide, -   [200]     N-(6-butyryl-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl)-2-fluoro-benzamide, -   [201]     N-(6-benzenesulfonylamino-5,6,7,8-tetrahydro-quinazolin-2-yl)-4-fluoro-benzamide, -   [202]     N-[6-(5-chloro-thiophene-2-sulfonylamino)-5,6,7,8-tetrahydro-quinazolin-2-yl]-4-fluoro-benzamide, -   [203] naphthalene-1-carboxylic acid     (6-hexanoyl-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl)-amide, -   [204]     N-(6-propionyl-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl)-2-trifluoromethyl-benzamide, -   [205]     N-[6-(2-ethyl-butyryl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-4-methyl-benzamide, -   [206]     2-fluoro-N-[6-(3-trifluoromethyl-benzenesulfonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-benzamide, -   [207] 5-benzyl-furan-2-carboxylic acid     {2-[(thiophene-2-carbonyl)-amino]-5,6,7,8-tetrahydro-quinazolin-6-yl}-amide, -   [208] thiophene-2-carboxylic acid     {6-[2-(2,5-dimethyl-phenyl)-acetylamino]-5,6,7,8-tetrahydro-quinazolin-2-yl}-amide, -   [210]     4-fluoro-N-[6-(propane-1-sulfonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-benzamide, -   [211]     2-[2-(3-fluoro-benzoylamino)-7,8-dihydro-5H-pyrido[4,3-d]pyrimidine-6-sulfonyl]-benzoic     acid methyl ester, -   [212]     3,5-dichloro-N-[6-(5-[1,2]dithiolan-3-yl-pentanoyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-benzamide, -   [213] thiophene-2-carboxylic acid     [6-(2-phenoxy-butyrylamino)-5,6,7,8-tetrahydro-quinazolin-2-yl]-amide, -   [214] thiophene-2-carboxylic acid     {6-[2-(4-methoxyphenyl)-acetylamino]-5,6,7,8-tetrahydro-quinazolin-2-yl}-amide, -   [215]     N-(6-cyclohexanecarboxylic-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl)-2-trifluoromethyl-benzamide, -   [216]     N-[6-(2,4-dimethyl-thiazole-5-sulfonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-2-trifluoromethyl-benzamide, -   [217] 2-thiophen-2-yl-thiazole-4-carboxylic acid     {2-[(thiophene-2-carbonyl)-amino]-5,6,7,8-tetrahydro-quinazolin-6-yl}-amide, -   [219] thiophene-2-carboxylic acid     {6-[3-(3-trifluoromethyl-phenyl)-acryloylamino]-5,6,7,8-tetrahydro-quinazolin-2-yl}-amide, -   [220] thiophene-2-carboxylic acid     [6-(5-phenyl-pentanoylamino)-5,6,7,8-tetrahydro-quinazolin-2-yl]-amide, -   [221] thiophene-2-carboxylic acid     [6-(2-chloro-5-trifluoromethyl-benzoylamino)-5,6,7,8-tetrahydro-quinazolin-2-yl]-amide, -   [222]     4-fluoro-N-[6-(2,3,5,6-tetramethyl-benzenesulfonylamino)-5,6,7,8-tetrahydro-quinazolin-2-yl]-benzamide, -   [223]     4-fluoro-N-[6-(4-methyl-octanoyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-benzamide, -   [224]     2-{2-[(thiophene-2-carbonyl)-amino]-5,6,7,8-tetrahydro-quinazolin-6-ylsulfamoyl}-benzoic     acid methyl ester, -   [225]     [(3-methyl-1-{2-[(thiophene-2-carbonyl)-amino]-5,6,7,8-tetrahydro-quinazolin-6-ylcarbamoyl}-butylcarbamoyl)-methyl]-carbamic     acid benzyl ester, -   [226]     3-chloro-N-(6-pentanoyl-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl)-benzamide, -   [227]     4-fluoro-N-[6-(5-oxo-5-phenyl-pentanoylamino)-5,6,7,8-tetrahydro-quinazolin-2-yl]-benzamide, -   [228] thiophene-2-carboxylic acid     [6-(3-phenyl-acryloylamino)-5,6,7,8-tetrahydro-quinazolin-2-yl]-amide, -   [229]     N-[6-(5-[1,2]dithiolan-3-yl-pentanoylamino)-5,6,7,8-tetrahydro-quinazolin-2-yl]-4-fluoro-benzamide, -   [230] benzoic acid     2-(2-{2-[(thiophene-2-carbonyl)-amino]-5,6,7,8-tetrahydro-quinazolin-6-ylcarbamoyl}-ethyl)-phenyl     ester, -   [231]     4-fluoro-N-[6-(2-methyl-5-nitro-benzenesulfonylamino)-5,6,7,8-tetrahydro-quinazolin-2-yl]-benzamide, -   [232]     4-chloro-N-[6-(2-phenoxy-acetyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-benzamide, -   [234]     N-[6-(5-bromo-thiophene-2-carbonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-2-fluoro-benzamide, -   [235]     4-fluoro-N-[6-(5-fluoro-2-methyl-benzenesulfonylamino)-5,6,7,8-tetrahydro-quinazolin-2-yl]-benzamide, -   [236]     N-[6-(4-acetylamino-benzenesulfonylamino)-5,6,7,8-tetrahydro-quinazolin-2-yl]-4-fluoro-benzamide, -   [237] thiophene-2-carboxylic acid     [6-(2-trifluoromethyl-benzoylamino)-5,6,7,8-tetrahydro-quinazolin-2-yl]-amide, -   [238]     3,4-difluoro-N-[6-(quinoline-6-carbonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-benzamide, -   [239]     {1-[2-(4-fluoro-benzoylamino)-5,6,7,8-tetrahydro-quinazolin-6-ylcarbamoyl]-2-phenyl-ethyl}-carbamic     acid tert-butyl ester, -   [240] thiophene-2-carboxylic acid     [6-(2-methyl-benzoylamino)-5,6,7,8-tetrahydro-quinazolin-2-yl]-amide, -   [241]     3-chloro-N-{6-[3-(2-oxo-benzooxazol-3-yl)-propionyl]-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl}-benzamide, -   [242]     3-chloro-N-[6-(5-chloro-thiophene-2-sulfonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-benzamide, -   [243]     3,5-dichloro-N-[6-(4-methoxy-benzenesulfonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-benzamide, -   [244]     4-tert-butyl-N-[6-(5-methyl-isoxazole-3-carbonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-benzamide, -   [245]     N-[6-(5-bromo-2-methoxy-benzenesulfonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-4-methyl-benzamide, -   [246]     4-tert-butyl-N-{6-[3-(2-hydroxyphenyl)-propionyl]-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl}-benzamide, -   [247]     4-fluoro-N-[6-(2-phenyl-butyrylamino)-5,6,7,8-tetrahydro-quinazolin-2-yl]-benzamide, -   [248]     4-tert-butyl-N-[6-(4-propyl-benzoyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-benzamide, -   [249] thiophene-2-carboxylic acid     [6-(2-bromo-benzoylamino)-5,6,7,8-tetrahydro-quinazolin-2-yl]-amide, -   [250]     2-methoxy-N-[6-(6-phenoxy-pyridine-3-carbonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-benzamide, -   [251]     N-[6-(4-acetylamino-benzenesulfonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-4-ethyl-benzamide, -   [252]     3,5-dichloro-N-[6-(4-fluoro-benzenesulfonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-benzamide, -   [253]     N-[6-(1-benzenesulfonyl-1H-indole-2-carbonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-4-fluoro-benzamide, -   [255]     N-[6-(3-chloro-benzenesulfonylamino)-5,6,7,8-tetrahydro-quinazolin-2-yl]-4-fluoro-benzamide,

in each case optionally in the form of one of the pure stereoisomers thereof, in particular enantiomers or diastereomers, the racemates thereof or in the form of a mixture of stereoisomers, in particular the enantiomers and/or diastereomers, in any desired mixing ratio, or in each case in the form of corresponding salts or in each case in the form of corresponding solvates.

The present invention also provides a process for the production of substituted 5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl-compounds of the above-stated general formula I, in which X denotes an NR^(2a) group, according to which an N-protected piperidin-4-one of the general formula II,

in which PG denotes a protective group, is converted by reaction with dimethoxy-methyl-dimethyl-amine of the formula III

in an organic reaction medium to yield a compound of the general formula IV,

in which PG has the above-stated meaning, this latter compound is optionally purified and/or isolated, and is converted by reaction with guanidine of the formula V,

optionally in the form of a corresponding salt, in an organic reaction medium, optionally in the presence of at least one base to yield a compound of the general formula VI,

in which PG has the above-stated meaning, this latter compound is optionally purified and/or isolated, and is reacted in an organic reaction medium, optionally in the presence of at least one base and/or at least one catalyst, with a compound of the general formula R³—C(═O)—X¹ or a compound of the general formula (R³—C(═O))₂O, or by reaction with a compound of the general formula R³—C(═O)—OH in an organic reaction medium in the presence of at least one coupling agent, optionally in the presence of at least one base, or by reaction with a compound of the general formula R⁴—O—C(═O)—X^(1a) in an organic reaction medium, optionally in the presence of at least one base, wherein R³ and R⁴ in each case have the above-stated meaning and X¹ and X^(1a) in each case denote a leaving group, to yield a compound of the general formula VII,

in which PG and R¹ have the above-stated meaning, this latter compound is optionally purified and/or isolated, and by elimination of the protective group PG is converted to yield an appropriately substituted compound of the general formula VIII,

optionally in the form of a corresponding salt, this latter compound is optionally purified and/or isolated, and is converted by reaction with a compound of the general formula R⁵—C(═O)—X² or (R⁵—C(═O))₂O, in which R⁵ in each case has the above-stated meaning and X² denotes a leaving group, in an organic reaction medium, optionally in the presence of at least one base and/or in the presence at least one catalyst,

or by reaction with a compound of the general formula R⁶—SO₂—X³, in which R⁶ has the above-stated meaning and X³ denotes a leaving group, in an organic reaction medium, optionally in the presence of at least one base, or by reaction with a compound of the general formula R⁵—COOH, in which R⁵ has the above-stated meaning, in an organic reaction medium, in the presence of at least one suitable coupling agent, optionally in the presence of at least one base, to yield a compound of the general formula IX

in which R¹ and R^(2a) have the above-stated meaning, this latter compound is optionally purified and/or isolated, and optionally converted to yield a corresponding salt and this is optionally purified and/or isolated,

or piperidin-4-one of the general formula X

optionally in the form of a corresponding salt, is converted by reaction with a compound of the general formula R⁵—C(═O)—X2 or (R⁵—C(═O))2O, in which R5 in each case has the above-stated meaning and X2 denotes a leaving group, in an organic reaction medium, optionally in the presence of at least one base and/or in the presence of at least one catalyst, or by reaction with a compound of the general formula R6-SO2-X3, in which R6 has the above-stated meaning and X3 denotes a leaving group, in an organic reaction medium, optionally in the presence of at least one base, or by reaction with a compound of the general formula R5-COOH, in which R5 has the above-stated meaning, in an organic reaction medium, in the presence of a suitable coupling agent, optionally in the presence of at least one base, to yield a compound of the general formula XI,

in which R^(2a) has the above-stated meaning, this latter compound is optionally purified and/or isolated, and is converted by reaction with dimethoxy-methyl-dimethyl-amine of the formula III

in an organic reaction medium to yield a compound of the general formula XII,

in which R^(2a) has the above-stated meaning, this compound is optionally purified and/or isolated, and is converted with guanidine of the formula V,

optionally in the form of a corresponding salt, in an organic reaction medium, optionally in the presence of at least one base, to yield a compound of the general formula XIII

this compound is optionally purified and/or isolated, and is reacted in an organic reaction medium, optionally in the presence of at least one base and/or at least one catalyst, with a compound of the general formula R³—(C═O)—X¹ or a compound of the general formula (R³—C(═O))₂O, or by reaction with a compound of the general formula R³—COOH in an organic reaction medium in the presence of at least one coupling agent, optionally in the presence of at least one base, or by reaction with a compound of the general formula R⁴—O—C(═O)—X^(1a) in an organic reaction medium, optionally in the presence of at least one base, wherein R³ and R⁴ in each case have the above-stated meaning and X¹ and X^(1a) denote a leaving group, to yield a compound of the general formula XIV

in which R¹ and R^(2a) have the above-stated meaning, and this latter compound is optionally purified and/or isolated, and optionally converted to yield a corresponding salt and this salt is optionally purified and/or isolated.

The process according to the invention for the production of substituted 5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl compounds of the above-stated general formula I, in which X denotes an —NR^(2a) group starting from N-protected piperidin-4-one, is also reproduced in the following scheme I.

In Step 1, piperidin-4-one, which is provided on the nitrogen atom with a protective group (PG), is firstly reacted with dimethoxymethyl-dimethyl-amine in an organic reaction medium, preferably toluene and/or benzene, to yield at least one compound of the above-stated general formula IV, which is preferably used without further working up in Step 2.

Dimethoxymethyl-dimethyl-amine, piperidin-4-one and N-protected piperidone are commercially obtainable, but may also be produced using conventional methods known to the person skilled in the art. Examples of suitable protective groups which may be considered for piperidone are trifluoroacetamide, methoxycarbonyl, ethoxycarbonyl, tert-butoxycarbonyl, benzyloxycarbonyl, allyloxycarbonyl or 9-fluorenylmethoxycarbonyl. Suitable reagents and methods for introducing these protective groups are known to the person skilled in the art.

In Step 2, the respective compound of the general formula IV is reacted optionally in the presence of at least one organic base and/or at least one organometallic base, preferably in the presence of sodium ethanolate and/or sodium methanolate, in an organic reaction medium, preferably methanol and/or ethanol, with guanidine of the formula V, optionally in the form of a corresponding salt such as for example guanidine hydrochloride, to yield the respective compound of the above-stated general formula VI.

Guanidine and the corresponding salts thereof are commercially obtainable, but may also be produced using conventional methods known to the person skilled in the art.

In Step 3, the respective compound of the general formula VI is reacted under conventional conditions known to the person skilled in the art in an organic reaction medium such as for example pyridine by acylation with at least one compound of the general formula R³—C(═O)—X¹ or at least one compound of the general formula (R³—C(═O))₂O, optionally in the presence of at least one organic base and/or at least one inorganic base, which may preferably be selected from the group consisting of diisopropylethylamine, triethylamine, pyridine and diethylamine, optionally in the presence of at least one catalyst, preferably in the presence of dimethylaminopyridine (DMAP), to yield the respective compound of the general formula VII.

Alternatively, the reaction of the respective compound of the general formula VI may also proceed with at least one carboxylic acid of the general formula R³—COOH, in which R³ in each case has the above-stated meaning, in an organic reaction medium, preferably selected from the group consisting of dichloromethane, DMF, THF and acetonitrile, optionally in the presence of at least one conventional coupling agent known to the person skilled in the art, preferably selected from the group consisting of N,N′-carbonyldiimidazole (CDI), N,N′-dicyclohexylcarbodiimide (DCC) and N-ethyl-N′-[3-(dimethylamino)-propyl]-carbodiimide (EDCI), or in the presence of 1-hydroxy-7-azabenzotriazole (HOAt) and at least one organic base such as for example diisopropylethylamine (DIPEA).

A further possible alternative is for the reaction to proceed with at least one compound of the general formula R⁴—O—C(═O)—X^(1a), in which R⁴ has the above-stated meaning and X^(1a) denotes a leaving group, in an organic reaction medium such as for example acetonitrile, DMF or dichloromethane, optionally in the presence of at least one base for example selected from the group consisting of aqueous potassium carbonate, sodium hydrogencarbonate, sodium hydroxide solution, diisopropylethylamine, triethylamine, pyridine and diethylamine.

The respective compound of the general formula VII is converted by elimination of the respective protective group (PG) in Step 4 under conventional conditions known to the person skilled in the art to yield the respective compound of the above-stated general formula VIII, optionally in the form of a corresponding salt such as for example trifluoroacetate.

For example, elimination of the above-stated protective groups may proceed in the presence of at least one inorganic base, acid or Lewis acid, such as for example potassium carbonate, lithium hydroxide, potassium hydroxide, sulfuric acid, hydrobromic acid, hydrofluoric acid, hydrochloric acid, boron trifluoride etherate or boron trichloride, at least one organic acid such as for example trifluoroacetic acid, trifluoromethanesulfonic acid or acetic acid, or in the presence of at least one organic base, such as for example morpholine, triethylamine, diethylamine, diisopropylethylamine or pyridine or by hydrogenation.

The respective compound of the above-stated general formula VIII is reacted in Step 5 under conventional conditions known to the person skilled in the art in an organic reaction medium, such as for example pyridine, by acylation with at least one compound of the general formula R⁵—C(═O)—X² or at least one compound of the general formula (R⁵—C(═O))₂O, in which R⁵ in each case has the above-stated meaning and X² denotes a conventional leaving group familiar to the person skilled in the art, preferably a halogen such as for example chlorine, optionally in the presence of at least one organic base and/or at least one inorganic base, preferably at least one base selected from the group consisting of diisopropylethylamine, triethylamine, pyridine and diethylamine, optionally in the presence of at least one catalyst, preferably dimethylaminopyridine (DMAP), or by sulfonylation with at least one sulfonyl compound of the general formula R⁶—S(═O)₂—X³, in which R⁶ in each case has the above-stated meaning and X³ denotes a conventional leaving group familiar to the person skilled in the art, preferably a halogen such as for example chlorine, optionally in the presence of at least one organic base and/or at least one inorganic base, preferably at least one base selected from the group consisting of sodium hydrogencarbonate, diisopropylethylamine, triethylamine, pyridine and diethylamine, or by reaction with at least one carboxylic acid of the general formula R⁵—COOH, in which R⁵ in each case has the above-stated meaning, in an organic reaction medium, preferably selected from the group consisting of dichloromethane, DMF, THF and acetonitrile, optionally in the presence of at least one conventional coupling agent known to the person skilled in the art, preferably selected from the group consisting of N,N′-carbonyldiimidazole (CDI), N,N′-dicyclohexylcarbodiimide (DCC) and N-ethyl-N′-[3-(dimethylamino)-propyl]-carbodiimide (EDCI), or in the presence of 1-hydroxy-7-azabenzotriazole (HOAt) and at least one organic base such as for example diisopropylethylamine (DIPEA) to yield the respective substituted 5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl compound of the above-stated general formula I.

Alternatively, the substituted 5,6,7,8-tetrahydropyrido[4,3-d]-pyrimidin-2-yl compounds according to the invention of the above-stated general formula I, in which X denotes an —NR^(2a) group, are produced starting from piperidin-4-one. The corresponding process is illustrated in Scheme II.

The respective compound of the above-stated general formula XI is obtained starting from piperidin-4-one of the general formula X, optionally in the form of a corresponding salt such as for example the hydrochloride, under conventional conditions known to the person skilled in the art in an organic reaction medium, such as for example pyridine, by acylation with at least one compound of the general formula R⁵—C(═O)—X² or (R⁵—C(═O))₂O in which R⁵ in each case has the above-stated meaning and X² denotes a conventional leaving group familiar to the person skilled in the art, preferably a halogen such as for example chlorine, optionally in the presence of at least one organic base and/or at least one inorganic base, preferably at least one base selected from the group consisting of diisopropylethylamine, triethylamine, pyridine and diethylamine, optionally in the presence of at least one catalyst, preferably DMAP, or by sulfonylation with at least one compound of the general formula R⁶—S(═O)₂—X³, in which R⁶ has the above-stated meaning and X³ denotes a conventional leaving group familiar to the person skilled in the art, preferably a halogen such as for example chlorine, in the presence of at least one organic base and/or at least one inorganic base, preferably at least one base selected from the group consisting of sodium hydrogencarbonate, diisopropylethylamine, triethylamine, pyridine and diethylamine, or by reaction with a carboxylic acid of the general formula R⁵—COOH in an organic reaction medium, preferably selected from the group consisting of dichloromethane, DMF, THF and acetonitrile, in the presence of a conventional coupling agent known to the person skilled in the art, preferably selected from the group consisting of CDI, DCC and EDCI, or optionally in the presence of HOAt and at least one organic base such as for example DIPEA.

The resultant compound of the above-stated general formula XI is then reacted with dimethoxy-methyl-dimethyl-amine of the formula III in an organic reaction medium, preferably toluene and/or benzene, to yield the respective compound of the above-stated general formula XII, which compound is preferably converted without further working up in the presence of at least one organic base and/or at least one organometallic base, preferably sodium ethanolate and/or sodium methanolate, in an organic reaction medium, preferably methanol and/or ethanol, with guanidine of the above-stated formula V, optionally in the form of a corresponding salt such as for example guanidine hydrochloride, to yield the respective compound of the above-stated general formula XIII.

Reaction of the respective compound of the general formula XIII with at least one compound of the general formula R⁴—O—(C═O)—X^(1a) or at least one compound of the general formula (R³—C(═O))₂O or a compound of the general formula R³—C(═O)—X¹, in which R³ and R⁴ in each case have the above-stated meaning and X¹ and X^(1a) denote a conventional leaving group familiar to the person skilled in the art, preferably a halogen such as for example chlorine, in the presence of at least one base, preferably selected from the group consisting of aqueous potassium carbonate, sodium hydrogencarbonate, sodium hydroxide solution, diisopropylethylamine, triethylamine, pyridine, diethylamine, optionally in an organic reaction medium, preferably selected from the group consisting of acetonitrile, DMF and dichloromethane, then leads to the respective substituted 5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl compounds of the above-stated general formula I, in which X denotes an —NR^(2a) group and R¹ has the above-stated meaning.

Alternatively, reaction of the respective compound of the general formula XIII may also proceed with at least one carboxylic acid of the general formula R³—COOH, in which R³ in each case has the above-stated meaning, in an organic reaction medium, preferably selected from the group consisting of dichloromethane, DMF, THF and acetonitrile, optionally in the presence of at least one conventional coupling agent known to the person skilled in the art, preferably selected from the group consisting of N,N′-carbonyldiimidazole (CDI), N,N′-dicyclohexylcarbodiimide (DCC) and N-ethyl-N′-[3-(dimethylamino)-propyl]-carbodiimide (EDCI), or in the presence of 1-hydroxy-7-azabenzotriazole (HOAt) and at least one organic base such as for example diisopropylethylamine (DIPEA).

The present invention also provides a process for the production of substituted 5,6,7,8-tetrahydro-quinazolin-2-yl compounds of the above-stated general formula I, in which X denotes a C(H)(NHR²) group, according to which 1,4-dioxa-spiro[4.5]dec-8-yl-amine of the formula C

is converted by reaction with a compound of the general formula R⁵—C(═O)—X⁴ or (R⁵—C(═O))₂O, in which R⁵ in each case has the above-stated meaning and X⁴ denotes a leaving group, in an organic reaction medium, optionally in the presence of at least one base and/or in the presence at least one catalyst, or by reaction with a compound of the general formula R⁶—SO₂—X⁵, in which R⁶ has the above-stated meaning and X⁵ denotes a leaving group, in an organic reaction medium, optionally in the presence of at least one base, or by reaction with a compound of the general formula R⁵—COOH, in which R⁵ has the above-stated meaning, in an organic reaction medium, in the presence of a suitable coupling agent, optionally in the presence of at least one base, to yield a compound of the general formula D

in which R² has the above-stated meaning, this latter compound is optionally purified and/or isolated, and converted by elimination of the acetal group in an organic reaction medium in the presence of water and at least one acid to yield a compound of the general formula E,

in which R² has the above-stated meaning, and this latter compound is converted by introduction of a protective group (PG¹) in an organic reaction medium to yield the compound of the general formula F

in which R² has the above-stated meaning and PG¹ denotes a protective group, this latter compound is optionally purified and/or isolated, and is converted by reaction with dimethoxymethyl-dimethyl-amine of the general formula III

in an organic reaction medium to yield a compound of the general formula G

in which R² and PG¹ have the above-stated meaning, and this latter compound is optionally purified and/or isolated, and optionally converted in the presence of at least one base in an organic reaction medium with a guanidine compound of the formula V, optionally in the form of a corresponding salt,

to yield a compound of the general formula H

this latter compound is optionally purified and/or isolated, and is converted by introduction of a protective group (PG2) in an organic reaction medium to yield a compound of the general formula I

in which R² and PG² have the above-stated meaning, this latter compound is optionally purified and/or isolated, and converted by reaction with a compound of the general formula R³—C(═O)—X⁶ or a compound of the general formula (R³—C(═O))₂O, in which R³ in each case has the above-stated meaning and X⁶ denotes a leaving group, or by reaction with a compound of the general formula R³COOH, in which R³ has the above-stated meaning, in an organic reaction medium in the presence of a coupling agent, optionally in the presence of at least one base, or by reaction with a compound of the general formula R⁴—O—C(═O)—X^(1a) in an organic reaction medium, optionally in the presence of a base, to yield a compound of the general formula J

in which R² and PG² have the above-stated meaning and R¹ has the above-stated meaning, this latter compound is optionally purified and/or isolated, and converted by elimination of the protective group to yield a 5,6,7,8-tetrahydro-quinazolin-2-yl compound of the general formula I, in which X denotes a C(H)(NHR²) group, this latter compound is optionally purified and/or isolated and then optionally converted to yield a corresponding salt, and this is optionally purified and/or isolated.

The process according to the invention for the production of substituted 5,6,7,8-tetrahydro-quinazolin-2-yl compounds of the above-stated general formula I, in which X denotes a C(H)(NHR²) group, is also reproduced in Scheme III below.

1,4-Dioxa-spiro[4.5]dec-8-yl-amine of the formula C may be produced using conventional methods known to the person skilled in the art, for example starting from 1,4-dioxa-spiro[4.5]decan-8-one, which is converted via reductive amination with benzylamine in an organic reaction medium, such as for example dichloromethane, in the presence of sodium cyanoborohydride or sodium triacetoxyborohydride or by reaction with hydroxylamine hydrochloride in the presence of an organic base, such as triethylamine or Amberlyst, in an organic reaction medium, such as ethanol, to yield the compound of the general formula B, in which R denotes a hydroxy group or a benzyl residue, which compound is optionally purified and/or isolated, and is reacted in the presence of at least one catalyst such as palladium on activated carbon (Pd(C)) by hydrogenation or by reduction with at least one metal hydride such as for example lithium aluminium hydride in an organic reaction medium, preferably ethanol and/or THF, to yield 1,4-dioxa-spiro[4.5]dec-8-yl-amine of the formula C.

The compound 1,4-dioxa-spiro[4.5]dec-8-yl-amine of the formula C is then reacted under conventional conditions known to the person skilled in the art in an organic reaction medium, such as for example pyridine, by acylation with a compound of the general formula R⁵—C(═O)—X⁴ or (R⁵—C(═O))₂O, in which R⁵ has the above-stated meaning, and X⁴ denotes a conventional leaving group known to the person skilled in the art, preferably halogen, particularly preferably chlorine, optionally in the presence of at least one organic base and/or at least one inorganic base, preferably at least one base selected from the group consisting of diisopropylethylamine, triethylamine, pyridine and diethylamine, optionally in the presence of at least one catalyst, preferably DMAP, or by sulfonylation of the compound 1,4-dioxa-spiro[4.5]dec-8-yl-amine of the formula C with at least one sulfonyl compound of the general formula R⁶—SO₂—X⁵, in which R⁶ has the above-stated meaning, and X⁵ denotes a conventional leaving group known to the person skilled in the art, preferably halogen, particularly preferably chlorine, in an organic reaction medium, preferably acetonitrile and/or dichloromethane, in the presence of at least one organic base and/or at least one inorganic base, preferably in the presence of at least one base selected from the group consisting of potassium carbonate, sodium hydrogencarbonate, diisopropylethylamine, triethylamine, pyridine and diethylamine, or by reaction of the compound 1,4-dioxa-spiro[4.5]dec-8-yl-amine of the formula C with at least one carboxylic acid of the general formula R⁵—COOH, in which R⁵ has the above-stated meaning, in at least one organic reaction medium, preferably selected from the group consisting of dichloromethane, DMF, THF and acetonitrile, in the presence of at least one conventional coupling agent known to the person skilled in the art to yield the corresponding compound of the general formula D.

Corresponding coupling agents which lead to the formation of an amide grouping are for example CDI, DCC or EDCI. Alternatively, HOAt, in conjunction with at least one organic base, such as for example DIPEA, may also be considered.

The respective compound of the general formula D is then converted by elimination of the acetal protective group under conventional conditions known to the person skilled in the art to yield a compound of the general formula E, preferably by elimination of the acetal protective group in an organic reaction medium, preferably dichloromethane and/or methanol, in the presence of water with at least one inorganic acid and/or at least one organic acid, preferably selected from the group consisting of methanolic hydrochloric acid, hydrochloric acid, p-toluenesulfonic acid, trifluoroacetic acid, acetic acid, and citric acid, or in the presence of a Lewis acid.

Starting from a compound of the general formula E, the respective compound F is obtained by introduction of a protective group (PG1).

Suitable protective groups (PG1) are for example trifluoroacetamide, methoxycarbonyl, ethoxycarbonyl, tert-butoxycarbonyl, benzyloxycarbonyl, allyloxycarbonyl and 9-fluorenylmethoxycarbonyl. Suitable reagents and processes for introducing these protective groups are known to the person skilled in the art.

The respective compound of the general formula F is then reacted with dimethoxymethyl-dimethyl-amine of the general formula III in an organic reaction medium, preferably toluene and/or benzene, to yield the corresponding compound of the general formula G, which is preferably reacted without further working up in the presence of at least one organic base or at least one organometallic base, preferably in the presence of sodium ethanolate and/or sodium methanolate, in an organic reaction medium, preferably methanol and/or ethanol, with guanidine of the general formula V, preferably in the form of a corresponding salt, such as for example guanidine hydrochloride, to yield the respective compound of the general formula H.

The protective group may optionally be partially eliminated in the process and is reintroduced under conventional conditions known to the person skilled in the art, such that the respective compound of the formula I is obtained. The protective group (PG2) introduced may be identical to or different from, preferably identical to, the above-stated protective group (PG1).

The respective compound of the above-stated general formula I is then reacted under conventional conditions known to the person skilled in the art in an organic reaction medium such as for example pyridine by acylation with at least one compound of the general formula R³—C(═O)—X⁶ or a compound of the general formula (R³—C(═O))₂O, in which R³ in each case has the above-stated meaning and X⁶ denotes a conventional leaving group known to the person skilled in the art, preferably halogen, particularly preferably chlorine, in an organic reaction medium, optionally in the presence of at least one organic base and/or at least one inorganic base, preferably a base selected from the group consisting of diisopropylethylamine, triethylamine, pyridine and diethylamine, optionally in the presence of at least one catalyst, preferably DMAP, or by reaction with at least one carboxylic acid R³—COOH, in which R³ has the above-stated meaning, in an organic reaction medium, preferably selected from the group consisting of dichloromethane, DMF, THF and acetonitrile, in the presence of at least one conventional coupling agent, preferably selected from the group consisting of CDI, DCC and EDCI, or in the presence of HOAt and at least one organic base such as for example DIPEA to yield the corresponding compound of the general formula J.

A further possible alternative is for the reaction to proceed with at least one compound of the general formula R⁴—O—C(═O)—X^(1a), in which R⁴ has the above-stated meaning and Xla denotes a leaving group, in an organic reaction medium, such as for example acetonitrile, DMF or dichloromethane, optionally in the presence of at least one base for example selected from the group consisting of aqueous potassium carbonate, sodium hydrogencarbonate, sodium hydroxide solution, diisopropylethylamine, triethylamine, pyridine and diethylamine.

The respective compound of the general formula J is then converted by elimination of the protective group (PG2) under conventional conditions known to the person skilled in the art to yield the respective substituted 5,6,7,8-tetrahydro-quinazolin-2-yl compound of the above-stated general formula I, in which X denotes a C(H)(NHR²) group.

Elimination of the above-stated protective group (PG2) may proceed for example in the presence of an inorganic base, acid or Lewis acid, such as potassium carbonate, lithium hydroxide, potassium hydroxide, sulfuric acid, hydrobromic acid, hydrofluoric acid, hydrochloric acid, boron trifluoride etherate, boron trichloride, an organic acid such as trifluoroacetic acid, trifluoromethanesulfonic acid, acetic acid, or in the presence of an organic base, such as morpholine, triethylamine, diethylamine, diisopropylethylamine, pyridine or by hydrogenation.

The compounds of the general formulae R³—C(═O)—X¹, R⁵—C(═O)—X², R⁵—C(═O)—X⁴, R³—C(═O)—X⁶, (R³—C(═O))₂O, (R⁵—C(═O))₂O, R³—COOH, R⁵—COOH, R⁶—SO₂—X³, R⁶—SO₂—X⁵ and R⁴—O—(C═O)—X^(1a) are in each case commercially obtainable and/or may be produced using conventional methods known to the person skilled in the art.

The above-described reactions may in each case be performed under conventional conditions familiar to the person skilled in the art, for example with regard to temperature, pressure or the sequence of addition of the components. Optimum control of the process under the respective conditions may optionally be established by the person skilled in the art by simple preliminary testing.

The intermediate and final products obtained by the above-described reactions may in each case, if desired and/or necessary, be purified and/or isolated by conventional methods known to the person skilled in the art. Suitable purification methods are, for example, extraction methods and chromatographic methods such as column chromatography or preparative chromatography.

All the above-described process steps and in each case also the purification and/or isolation of intermediate or final products may be performed in part or entirely under an inert gas atmosphere, preferably under a nitrogen atmosphere.

If the substituted 5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl and 5,6,7,8-tetrahydro-quinazolin-2-yl compounds according to the invention of the above-stated general formula I are obtained after production thereof in the form of a mixture of the stereoisomers thereof, preferably in the form of the racemates thereof or other mixtures of the various enantiomers and/or diastereomers thereof, these may be resolved and optionally isolated using conventional methods known to the person skilled in the art. Examples are chromatographic separation processes, in particular liquid chromatography processes at standard pressure or at elevated pressure, preferably MPLC and HPLC processes, and fractional crystallisation processes. Individual enantiomers, for example diastereomeric salts formed by means of HPLC on a chiral phase or by means of crystallisation with chiral acids, for instance (+)-tartaric acid, (−)-tartaric acid or (+)-10-camphorsulfonic acid, may here in particular be separated from one another.

The substituted 5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl and 5,6,7,8-tetrahydro-quinazolin-2-yl compounds according to the invention of the above-stated general formula I and optionally in each case corresponding stereoisomers may be obtained using conventional methods known to the person skilled in the art in the form of corresponding salts, in particular in the form of corresponding physiologically acceptable salts, wherein the pharmaceutical preparation according to the invention may comprise one or more salts of one or more of these compounds.

The respective salts of the substituted 5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl and 5,6,7,8-tetrahydro-quinazolin-2-yl compounds according to the invention of the above-stated general formula I and corresponding stereoisomers may be obtained for example by reaction with one or more inorganic acids and/or one or more organic acids. Suitable acids may preferably be selected from the group consisting of perchloric acid, hydrochloric acid, hydrobromic acid, sulfuric acid, methanesulfonic acid, formic acid, acetic acid, oxalic acid, succinic acid, tartaric acid, mandelic acid, fumaric acid, lactic acid, citric acid, glutamic acid, saccharic acid, cyclohexanesulfamic acid, aspartame, monomethylsebacic acid, 5-oxo-proline, hexane-1-sulfonic acid, nicotinic acid, 2-aminobenzoic acid, 3-aminobenzoic acid or 4-aminobenzoic acid, 2,4,6-trimethylbenzoic acid, -lipoic acid, acetylglycine, hippuric acid, phosphoric acid, maleic acid, malonic acid and aspartic acid.

The substituted 5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl and 5,6,7,8-tetrahydro-quinazolin-2-yl compounds according to the invention of the above-stated general formula I and optionally corresponding stereoisomers and in each case the physiologically acceptable salts thereof may be obtained using conventional methods known to the person skilled in the art also in the form of the solvates thereof, in particular in the form of the hydrates thereof.

It has surprisingly been found that the substituted 5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl and 5,6,7,8-tetrahydro-quinazolin-2-yl compounds according to the invention are suitable for noradrenalin receptor regulation, in particular for inhibiting noradrenalin reuptake (noradrenalin uptake), for 5-HT receptor regulation, in particular for inhibiting 5-hydroxy-tryptophan reuptake (5-HT uptake), for mGluR5 receptor regulation and/or for batrachotoxin (BTX) receptor regulation and may therefore be used in particular as pharmaceutical active ingredients in pharmaceutical preparations for the prevention and/or treatment of disorders or diseases associated with these receptors or processes.

The substituted 5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl and 5,6,7,8-tetrahydro-quinazolin-2-yl compounds according to the invention of the above-stated general formula I and optionally corresponding stereoisomers and in each case the corresponding salts and solvates are toxicologically safe and are therefore suitable as pharmaceutical active ingredients in pharmaceutical preparations.

The present invention accordingly also provides a pharmaceutical preparation containing at least one substituted 5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl or 5,6,7,8-tetrahydro-quinazolin-2-yl compound according to the invention of the above-stated general formula I, in each case optionally in the form of one of the pure stereoisomers thereof, in particular enantiomers or diastereomers, the racemates thereof or in the form of a mixture of stereoisomers, in particular the enantiomers and/or diastereomers, in any desired mixing ratio, or in each case in the form of a corresponding salt, or in each case in the form of a corresponding solvate, and optionally one or more pharmaceutically acceptable auxiliary substances.

The pharmaceutical preparation according to the invention is suitable for noradrenalin receptor regulation, in particular for inhibiting noradrenalin reuptake (noradrenalin uptake), for 5-HT receptor regulation, in particular for inhibiting 5-hydroxy-tryptophan reuptake (5-HT uptake), for mGluR5 receptor regulation and/or for batrachotoxin (BTX) receptor regulation.

The pharmaceutical preparation according to the invention is preferably suitable for the prevention and/or treatment of disorders and/or diseases, which are mediated at least in part by noradrenalin receptors, 5-HT receptors, mGluR5 receptors and/or batrachotoxin (BTX) receptors.

The pharmaceutical preparation according to the invention is particularly preferably suitable for the prevention and/or treatment of pain, preferably of pain selected from the group consisting of acute pain, chronic pain, neuropathic pain and visceral pain, and/or for the prevention and/or treatment of migraine, depression, urinary incontinence, coughing, neurodegenerative diseases, preferably selected from the group consisting of Parkinson's disease, Huntington's chorea, Alzheimer's disease and multiple sclerosis, disorders of food intake, preferably selected from the group consisting of bulimia, anorexia, obesity and cachexia, cognitive dysfunction, preferably memory disorders, cognitive deficiency states (attention deficit syndrome, ADS), disorders of the nervous system, epilepsy, schizophrenia, cerebral ischaemia, muscle spasms, cramps, diarrhoea, pruritus, gastro-oesophageal reflux syndrome, panic attacks, alcohol and/or drug (in particular nicotine and/or cocaine) abuse and/or abuse of medicines, alcohol and/or drug (in particular nicotine and/or cocaine) dependency and/or dependency on medicines, preferably for the prevention and/or reduction of withdrawal symptoms associated with alcohol and/or drug dependency and/or dependency on medicines, for the prevention and/or reduction of a development of tolerance to medicines, in particular medicines based on opioids, for regulating food intake, for modulating locomotor activity, for regulating the cardiovascular system, for local anaesthesia, for anxiolysis, for increasing vigilance, for increasing libido, for diuresis, and/or for antinatriuresis.

The pharmaceutical preparation according to the invention is very particularly preferably suitable for the prevention and/or treatment of pain, preferably acute pain, chronic pain, neuropathic pain or visceral pain.

The present invention also provides the use of at least one substituted 5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl or 5,6,7,8-tetrahydro-quinazolin-2-yl compound according to the invention of the above-stated general formula I, in each case optionally in the form of one of the pure stereoisomers thereof, in particular enantiomers or diastereomers, the racemates thereof or in the form of a mixture of stereoisomers, in particular the enantiomers and/or diastereomers, in any desired mixing ratio, or in each case in the form of a corresponding salt, or in each case in the form of a corresponding solvate, and optionally one or more pharmaceutically compatible auxiliary substances for the production of a pharmaceutical preparation for noradrenalin receptor regulation, in particular for inhibiting noradrenalin reuptake (noradrenalin uptake), for 5-HT receptor regulation, in particular for inhibiting 5-hydroxy-tryptophan reuptake (5-HT uptake), for mGluR5 receptor regulation and/or for batrachotoxin (BTX) receptor regulation.

The use is preferred of at least one substituted 5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl or 5,6,7,8-tetrahydro-quinazolin-2-yl compound according to the invention of the above-stated general formula I, in each case optionally in the form of one of the pure stereoisomers thereof, in particular enantiomers or diastereomers, the racemates thereof or in the form of a mixture of stereoisomers, in particular the enantiomers and/or diastereomers, in any desired mixing ratio, or in each case in the form of a corresponding salt, or in each case in the form of a corresponding solvate, and optionally one or more pharmaceutically compatible auxiliary substances for the production of a pharmaceutical preparation for the prevention and/or treatment of disorders and/or diseases which are mediated at least in part by noradrenalin receptors, 5-HT receptors, mGluR5 receptors and/or batrachotoxin (BTX) receptors.

The use is particularly preferred of at least one substituted 5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl or 5,6,7,8-tetrahydro-quinazolin-2-yl compound according to the invention of the above-stated general formula I, in each case optionally in the form of one of the pure stereoisomers thereof, in particular enantiomers or diastereomers, the racemates thereof or in the form of a mixture of stereoisomers, in particular the enantiomers and/or diastereomers, in any desired mixing ratio, or in each case in the form of a corresponding salt, or in each case in the form of a corresponding solvate, and optionally one or more pharmaceutically compatible auxiliary substances for the production of a pharmaceutical preparation for the prevention and/or treatment of pain, preferably of pain selected from the group consisting of acute pain, chronic pain, neuropathic pain and visceral pain, and/or for the prevention and/or treatment of migraine, depression, urinary incontinence, coughing, neurodegenerative diseases, preferably selected from the group consisting of Parkinson's disease, Huntington's chorea, Alzheimer's disease and multiple sclerosis, disorders of food intake, preferably selected from the group consisting of bulimia, anorexia, obesity and cachexia, cognitive dysfunction, preferably memory disorders, cognitive deficiency states (attention deficit syndrome, ADS), disorders of the nervous system, epilepsy, schizophrenia, cerebral ischaemia, muscle spasms, cramps, diarrhoea, pruritus, gastro-oesophageal reflux syndrome, panic attacks, alcohol and/or drug abuse and/or abuse of medicines, alcohol and/or drug dependency and/or dependency on medicines, preferably for the prevention and/or reduction of withdrawal symptoms associated with alcohol and/or drug dependency and/or dependency on medicines, for the prevention and/or reduction of the development of tolerance to medicines, in particular medicines based on opioids, for regulating food intake, for modulating locomotor activity, for regulating the cardiovascular system, for local anaesthesia, for anxiolysis, for increasing vigilance, for increasing libido, for diuresis, and/or for antinatriuresis.

The use is very particularly preferred of at least one substituted 5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl or 5,6,7,8-tetrahydro-quinazolin-2-yl compound according to the invention of the above-stated general formula I, in each case optionally in the form of one of the pure stereoisomers thereof, in particular enantiomers or diastereomers, the racemates thereof or in the form of a mixture of stereoisomers, in particular the enantiomers and/or diastereomers, in any desired mixing ratio, or in each case in the form of a corresponding salt, or in each case in the form of a corresponding solvate, and optionally one or more pharmaceutically compatible auxiliary substances for the production of a pharmaceutical preparation for the prevention and/or treatment of pain, preferably of acute pain, chronic pain, neuropathic pain or visceral pain.

The pharmaceutical preparation according to the invention is suitable for administration to adults and children including small children and babies.

The pharmaceutical preparation according to the invention may be formulated as a liquid, semisolid or solid dosage form, for example in the form of solutions for injection, drops, succi, syrups, sprays, suspensions, tablets, patches, capsules, dressings, suppositories, ointments, creams, lotions, gels, emulsions, aerosols or in multiparticulate form, for example in the form of pellets or granules, optionally pressed into tablets, packaged in capsules or suspended in a liquid, and may also be administered as such.

In addition to at least one substituted 5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl or 5,6,7,8-tetrahydro-quinazolin-2-yl compound according to the invention of the above-stated general formula I, optionally in the form of the pure stereoisomer thereof, in particular enantiomer or diastereomer, the racemate thereof or in the form of mixtures of the stereoisomers, in particular the enantiomers or diastereomers, in any desired mixing ratio, or optionally in the form of a corresponding salt or in each case in the form of a corresponding solvate, the pharmaceutical preparation according to the invention conventionally contains further physiologically acceptable pharmaceutical auxiliary substances, which may preferably be selected from the group consisting of matrix materials, fillers, solvents, diluents, surface-active substances, dyes, preservatives, disintegrants, slip agents, lubricants, aromas and binders.

Selection of the physiologically acceptable auxiliary substances and the quantities thereof which are to be used depends upon whether the pharmaceutical preparation is to be administered orally, subcutaneously, parenterally, intravenously, intraperitoneally, intradermally, intramuscularly, intranasally, buccally, rectally or topically, for example onto infections of the skin, mucous membranes or eyes. Preparations in the form of tablets, coated tablets, capsules, granules, pellets, drops, succi and syrups are preferred for oral administration, while solutions, suspensions, readily reconstitutible dried preparations and sprays are preferred for parenteral, topical and inhalatory administration.

The substituted 5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl or 5,6,7,8-tetrahydro-quinazolin-2-yl compounds used in the pharmaceutical preparation according to the invention in a depot in dissolved form or in a dressing, optionally with the addition of skin penetration promoters, are suitable percutaneous administration preparations.

Orally or percutaneously administrable formulations may also release the respective substituted 5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl or 5,6,7,8-tetrahydro-quinazolin-2-yl compounds in delayed manner.

Production of the pharmaceutical preparations according to the invention proceeds with the assistance of conventional means, devices, methods and processes known from the prior art, such as are described for example in “Remington's Pharmaceutical Sciences”, ed. A. R. Gennaro, 17th ed., Mack Publishing Company, Easton, Pa. (1985), in particular in part 8, chapters 76 to 93. The corresponding description is hereby introduced as a reference and is deemed to be part of the disclosure.

The quantity of the respective substituted 5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl or 5,6,7,8-tetrahydro-quinazolin-2-yl compound to be administered to the patient may vary and is for example dependent on the weight or age of the patient and on the mode of administration, the indication and the severity of the complaint. Conventionally, 0.005 to 5000 mg/kg, preferably 0.05 to 500 mg/kg, particularly preferably 0.05 to 75 mg/kg of patient body weight of at least one such compound are administered.

Pharmacological Methods:

I. Method for Determining Noradrenalin and 5-HT Uptake Inhibition:

Synaptosomes from rat brain regions are freshly isolated for in vitro studies, as described in the publication “The isolation of nerve endings from brain” by E. G. Gray and V. P. Whittaker, J. Anatomy 96, pages 79-88, 1962. The corresponding literature description is hereby introduced as a reference and is deemed to be part of the disclosure.

The tissue (hypothalamus for the determination of noradrenalin uptake inhibition and medulla and pons for the determination of 5-HT uptake inhibition) is homogenised in ice-cooled 0.32 M sucrose (100 mg of tissue/1 mL) in a glass homogeniser with Teflon pestle using five complete up and down strokes at 840 revolutions/minute.

The homogenate is centrifuged at 4° C. for 10 minutes at 1000 g. After subsequent centrifugation at 17000 g for 55 minutes, the synaptosomes (P₂ fraction) are obtained, which are resuspended in 0.32 M glucose (0.5 mL/100 mg of original weight).

The particular uptake is measured in a 96-well microtitre plate. The volume is 250 μl and the incubation proceeds at room temperature (approx. 20-25° C.) under an O₂ atmosphere.

The incubation time is 7.5 minutes for [³H]-NA and 5 minutes for [³H]-5-HT.

The 96 samples are then filtered through a Unifilter GF/B microtitre plate (Packard) and washed with 200 mL of incubated buffer using a “Brabdel MPXRI-96T Cell-Harvester”. The Unifilter GF/B plate is dried for 1 hour at 55° C. The plate is then sealed with a Back seal (Packard) and 35 μl of scintillation fluid are added per well (Ultima Gold, Packard). After sealing with a top seal (Packard) and establishing an equilibrium (around 5 hours), radioactivity is determined in a “Trilux 1450 Microbeta” (Wallac).

The quantity of protein used in the above determination corresponds to the values known from the literature, as for example described in “Protein measurement with the folin phenol reagent”, Lowry et al., J. Biol. Chem., 193, 265-275, 1951.

A detailed description of the method may additionally be found in the literature, for example in M. Ch. Frink, H.-H. Hennies, W. Engelberger, M. Haurand and B. Wilffert (1996) Arzneim.-Forsch./Drug Res. 46 (III), 11, 1029-1036.

The corresponding literature descriptions are hereby introduced in each case as a reference and are deemed to be part of the present disclosure.

The following characteristics were determined for the NA or 5-HT transporter:

NA uptake: Km=0.32±0.11 μM

5HT uptake: Km=0.084±0.011 μM

II. Method for Determining Affinity for the Batrachotoxin (BTX) Binding Site of the Sodium Channel:

Binding site 2 of the sodium channel is the so-called batrachotoxin (BTX) binding site. [³H]-Batrachotoxinin A20 benzoate (10 nM in the batch) is used as ligand. The ion channel particles (synaptosomes) are enriched from rat cerebrocortex, as described in the publication by Gray and Whittaker (E. G. Gray and V. P. Whittaker (1962) J. Anat. 76, 79-88. The corresponding description is hereby introduced as a reference and is deemed to be part of the present disclosure. The radioactivity measured in the presence of veratridine (3×10⁻⁴ M in the batch) is defined as non-specific binding.

The assay conditions are as published by Pauwels, Leysen and Laduron, as described in Eur. J. Pharmacol. 124, 291-298. The corresponding description is hereby introduced as a reference and is deemed to be part of the present disclosure.

At variance with this method, the total batch is reduced to 250 μl, such that the assay may be performed on 96-well microtitre plates. The incubation time in these microtitre plates amounts to two hours at room temperature (approx. 20-25° C.).

The following characteristics were determined for the K_(D) value of the binding site:

K_(D): 24.63±1.56 nM.

III. Method for Determining Affinity for the mGluR5 Receptor

Pig brain homogenate is produced by homogenisation (Polytron Pt 3000, Kinematica AG, 10,000 rpm (revolutions per minute) for 90 seconds) of pig brain hemispheres without medulla, cerebellum and pons in a buffer of pH 8.0 (30 mM Hepes, Sigma, order number H3375+1 tablet Complete Roche Diagnostics, order number 1836145 made up to 100 ml) in a ratio of 1:20 (brain weight/volume) and differential centrifugation at 900 g and 40,000 g. 450 μg of protein from brain homogenate is incubated in each case in 250 μl incubation batches in 96-well microtitre plates with 15 nM ³[H]-MPEP (Tocris, order number R1212) and the compounds to be investigated (in each case 10 μM in the test) in the above-stated buffer at room temperature for 60 minutes.

The batches are then filtered with the assistance of a Brandel Cell Harvester (Brandel, Grade Robotic 9600) on Unifilter plates with glass filter mats (Perkin Elmer, order number 6005177) and then rewashed 3 times with buffer of the above-stated composition using 250 μl per sample. The filter plates are then dried for 60 minutes at 55° C. Then 30 μl of Ultima Gold scintillating material (Packard BioScience, order number 6013159) is added per well and after 3 hours the samples are measured using the B counter (Microbial, Perkin Elmer). Nonspecific binding is determined by the addition of 10 μM 2-methyl-6-(phenylethynyl)-pyridine (Tocris, order number 1212).

The invention is explained below with reference to Examples. These explanations are given merely by way of example and do not restrict the general concept of the invention.

EXAMPLES

The yields of the compounds produced have not been optimised.

All temperatures are uncorrected.

The term “ether” means diethyl ether, “EE” ethyl acetate, “DCM” dichloromethane, “DMF” dimethylformamide, “DME” dimethoxyethane, “DMSO” dimethyl sulfoxide and “THF” tetrahydrofuran. The term “equivalents” means molar equivalents, “mp” melting point or melting range, “decomp.” decomposition, “RT” room temperature, i.e. approx. 20° C., “abs.” absolute (anhydrous), “rac.” racemic, “conc.” concentrated, “min” minutes, “h” hours, “d” days, “vol. %” percent by volume and “wt. %” weight percent and “M” is an indication of concentration in mol/l.

Further abbreviations:

DIPEA diisopropylethylamine HOAt 1-hydroxy-7-azabenzotriazole EDCI N-ethyl-N′-[3-(dimethylamino)-propyl]-carbodiimide DCC N,N′-dicyclohexylcarbodiimide DMA dimethoxymethyl-dimethyl-amine DMAP dimethylaminopyridine CDI N,N′-carbonyldiimidazole Pd(C) palladium on activated carbon

The chemicals and solvents used were purchased from conventional suppliers (Acros, Avocado, Aldrich, Bachem, Fluka, Lancaster, Maybridge, Merck, Sigma, TCI, Oakwood etc.) or synthesised by conventional methods familiar to the person skilled in the art.

Silica gel 60 (0.040-0.063 mm) from E. Merck, Darmstadt, was used as the stationary phase for the column chromatography.

Thin-layer chromatography was performed with pre-coated silica gel 60 F 254 HPTLC plates from E. Merck, Darmstadt.

The mobile solvent mixture ratios for chromatographic investigations are always stated in volume/volume.

Analysis was carried out by NMR and HPLC-MS.

General Method for the Production of Exemplary Substituted 5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl Compounds

The synthesis of 2-amino-7,8-dihydro-5H-pyrido[4,3-d]pyrimidine-6-carboxylic acid tert-butyl ester of the formula VI (PG=tert-butyloxycarbonyl, BOC) proceeded as described in detail hereinafter.

In Step 3 the compound VI was acylated by reaction with carboxylic acid chlorides of the general formula R³—(C═O)—Cl or carboxylic acid bromides of the general formula R³—(C═O)—Br, wherein the respective carboxylic acid chloride was optionally produced directly from the corresponding carboxylic acid R³—(C═O)—OH.

To this end, in Step 3 oxalyl chloride (5 equivalents) and a few drops of DMF were added to a solution of the respective carboxylic acid (1 equivalent) in CH₂Cl₂ and stirring was performed for 1 h at RT under nitrogen as inert gas. After removal of the solvent, the respective carboxylic acid chloride was dissolved in pyridine. If a carboxylic acid chloride or carboxylic acid bromide was used, this (1 equivalent) was dissolved directly in pyridine.

2-Amino-7,8-dihydro-5H-pyrido[4,3-d]pyrimidine-6-carboxylic acid tert-butyl ester of the formula VI (0.85 equivalents) was added to this solution at 0° C. and stirring was performed for 2 h at 0° C. and then for 2 h at RT under nitrogen as inert gas. After the addition of aqueous 1 M NaOH and stirring for 20 minutes, CH₂Cl₂ was added and the aqueous phase extracted with CH₂Cl₂. The combined organic phases were dried over Na₂SO₄. After filtration and removal of the solvent, purification was performed by means of column chromatography and the respective compound of the general formula VII was obtained.

In Step 4, trifluoroacetic acid (65 equivalents) was added to a solution of the Boc-protected compound of the general formula VII (1 equivalent) in CH₂Cl₂ under nitrogen as inert gas and stirring was performed for 2 h at RT. After removal of the solvent, the unprotected compounds of the general formula VIII were obtained, which were used without further working up in Step 5.

In Step 5, acylation of the compounds of the general formula VIII proceeded with carboxylic acid chlorides of the general formula R⁵—C(═O)—Cl, carboxylic acid bromides of the general formula R⁵—C(═O)—Br or by reaction with carboxylic acids of the general formula R⁵—C(═O)—OH.

For acylation by means of a carboxylic acid in Step 5, the respective compound VIII was dissolved in CH₂Cl₂ and DIPEA and the respective carboxylic acid (1 equivalent) were added. After cooling of the reaction mixture to 0° C., EDCI (1 equivalent) and HOAt (20 mg, 0.15 equivalents) were added. The reaction mixture was stirred for 1 h at 0° C. and then overnight at RT. After removal of the solvent, purification proceeded via preparative HPLC or column chromatography and the respective compound of the general formula IX was obtained.

For acylation by means of a carboxylic acid halide, the respective compound of the general formula VIII (1 equivalent) was dissolved in CH₂Cl₂, triethylamine (2 equivalents), a catalytic quantity of DMAP and the respective carboxylic acid halide (1 equivalent) were added and then stirring was performed overnight at RT. After removal of the solvent, purification proceeded via preparative HPLC or column chromatography and the respective compound of the general formula IX was obtained.

In Step 5, sulfonylation of the compounds of the general formula VIII proceeded with sulfonyl chlorides of the general formula R⁶—S(═O)₂—Cl.

For sulfonylation, the respective compound of the general formula VIII (1 equivalent) was dissolved in CH₂Cl₂ and triethylamine (2 equivalents) and the respective sulfonyl chloride (1 equivalent) were added at 0° C. The reaction mixture was stirred overnight at RT. After removal of the solvent, purification proceeded via preparative HPLC or column chromatography and the respective compound of the general formula IX was obtained.

Hereinafter, the above-described method for the production of substituted 5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl compounds is explained in detail with reference to a number of exemplary compounds:

Production of 2-amino-7,8-dihydro-5H-pyrido[4,3-d]pyrimidine-6-carboxylic Acid tert-butyl Ester

Dimethoxymethyl-dimethyl-amine (DMA) 35.5 ml (266 mmol) was added to a solution of 4-oxo-piperidine-1-carboxylic acid tert-butyl ester 10.59 g (53.14 mmol) in toluene (50 ml) with stirring and with nitrogen as inert gas and refluxing was performed for 3.5 h. After removal of the solvent, the product 3-dimethylaminomethylene-4-oxo-piperidine-1-carboxylic acid tert-butyl ester was obtained, which was used in the subsequent reaction without further purification.

Guanidine hydrochloride 7.07 g (74 mmol) was added at 0° C. to a solution of sodium 1.65 g (74 mmol) in absolute ethanol and stirring was performed for 2 h at RT under nitrogen as inert gas. 60 ml (60 mmol) of this reaction mixture were added to the solution of 3-dimethylaminomethylene-4-oxo-piperidine-1-carboxylic acid tert-butyl ester in 100 ml of absolute ethanol and refluxing was performed for 5 h. After removal of the solvent and purification by means of column chromatography, 2-amino-7,8-dihydro-5H-pyrido[4,3-d]pyrimidine-6-carboxylic acid tert-butyl ester 5.72 g (43% of theoretical) was obtained.

Example 5 3,5-Dichloro-N-[6-(3-trifluoromethyl-benzoyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-benzamide a) Production of 2-(3,5-dichloro-benzoylamino)-7,8-dihydro-5H-pyrido[4,3-d]pyrimidine-6-carboxylic Acid tert-butyl Ester

Oxalyl chloride 1184 μl (13.8 mmol) and two drops of DMF were added to a solution of 3,5-dichlorobenzoic acid 527 mg (2.76 mmol) in CH₂Cl₂ and stirring was performed for 1 h at RT under nitrogen as inert gas. After removal of the solvent, the 3,5-dichlorobenzoyl chloride was dissolved in pyridine (30 ml). 2-Amino-7,8-dihydro-5H-pyrido[4,3-d]pyrimidine-6-carboxylic acid tert-butyl ester 599 mg (2.39 mmol) was added to this solution at 0° C. and stirring was performed for 2 h at 0° C. and then for 2 h at RT under nitrogen as inert gas. After the addition of aqueous 1 M NaOH (40 ml) and stirring for 20 minutes, CH2Cl2 (50 ml) was added and the aqueous phase extracted with CH2Cl2 (3×20 ml). The combined organic phases were dried over Na2SO4. After filtration and removal of the solvent, purification was performed by means of column chromatography and the product 2-(3,5-dichloro-benzoylamino)-7,8-dihydro-5H-pyrido[4,3-d]pyrimidine-6-carboxylic acid tert-butyl ester 573 mg (1.35 mmol, 57% of theoretical) was obtained.

b) 3,5-Dichloro-N-[6-(3-trifluoromethyl-benzoyl)-5,6,7,8-tetra-hydropyrido[4,3-d]pyrimidin-2-yl]-benzamide

Trifluoroacetic acid 5.0 ml (65 mmol) was added to a solution of 2-(3,5-dichloro-benzoylamino)-7,8-dihydro-5H-pyrido[4,3-d]pyrimidine-6-carboxylic acid tert-butyl ester 404 mg (0.954 mmol) in CH₂Cl₂ (7 ml) under nitrogen as inert gas and stirring was performed for 2 h at RT. After removal of the solvent, the intermediate (3,5-dichloro-N-(5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl)-benzamide trifluoroacetate) was dissolved in CH₂Cl₂ (10 ml) and DIPEA 340 μl and 3-trifluoromethylbenzoic acid 200 mg (1.05 mmol) were added. After cooling the reaction mixture to 0° C., EDCI 201 mg (1.05 mmol) and HOAt 20 mg (0.15 mmol) were added. The reaction mixture was stirred for 1 h at 0° C. and then overnight at RT. After removal of the solvent, purification was performed by means of column chromatography and the product 3,5-dichloro-N-[6-(3-trifluoromethyl-benzoyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-benzamide 260 mg (0.53 mmol, 55% of theoretical) was obtained.

Example 145 N-[6-(3-chloro-thiophene-2-carbonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-2-ethoxy-benzamide a) Production of 2-(2-ethoxy-benzoylamino)-7,8-dihydro-5H-pyrido[4,3-d]pyrimidine-6-carboxylic Acid tert-butyl Ester

2-Amino-7,8-dihydro-5H-pyrido[4,3-d]pyrimidine-6-carboxylic acid tert-butyl ester 528 mg (2.11 mmol) was added at 0° C. to a solution of 2-ethoxybenzoic acid chloride 390 mg (2.11 mmol) in pyridine (25 ml) and stirring was performed for 2 h at 0° C. and then for 72 h at RT under nitrogen as inert gas. After the addition of aqueous 1 M NaOH (40 ml) and stirring for 20 minutes, CH₂Cl₂ (50 ml) was added and the aqueous phase extracted with CH₂Cl₂ (3×20 ml). The combined organic phases were dried over Na₂SO₄. After filtration and removal of the solvent, purification was performed by means of column chromatography and the product 2-(2-ethoxy-benzoylamino)-7,8-dihydro-5H-pyrido[4,3-d]pyrimidine-6-carboxylic acid tert-butyl ester 600 mg (1.51 mmol, 72% of theoretical) was obtained.

b) N-[6-(3-chloro-thiophene-2-carbonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-2-ethoxy-benzamide

Trifluoroacetic acid 3.6 ml (49 mmol) was added to a solution of 2-(2-ethoxy-benzoylamino)-7,8-dihydro-5H-pyrido[4,3-d]pyrimidine-6-carboxylic acid tert-butyl ester 300 mg (0.753 mmol) in CH₂Cl₂ (10 ml) under nitrogen as inert gas and stirring was performed for 2 h at RT. After removal of the solvent, the intermediate (2-ethoxy-N-(5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl)-benzamide trifluoroacetate) was dissolved in CH₂Cl₂ (10 ml) and DIPEA 225 μl and 3-chlorothiophene-2-carboxylic acid 129 mg (0.791 mmol) were added. After cooling the reaction mixture to 0° C., EDCI 158 mg (0.828 mmol) and HOAt 15 mg (0.11 mmol) were added. The reaction mixture was stirred for 1 h at 0° C. and then overnight at RT. After removal of the solvent, purification was performed by means of column chromatography and the product N-[6-(3-chloro-thiophene-2-carbonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-2-ethoxy-benzamide 170 mg (0.38 mmol, 51% of theoretical) was obtained.

Example 109 3-Chloro-N-[6-(2-methyl-benzoyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-benzamide a) Production of 2-(3-chloro-benzoylamino)-7,8-dihydro-5H-pyrido[4,3-d]pyrimidine-6-carboxylic Acid tert-butyl Ester

2-Amino-7,8-dihydro-5H-pyrido[4,3-d]pyrimidine-6-carboxylic acid tert-butyl ester 1202 mg (4.8 mmol) was added at 0° C. to a solution of 3-chlorobenzoic acid chloride 615 μl (4.8 mmol) in pyridine (25 ml) and stirring was performed for 2 h at 0° C. and then overnight at RT under nitrogen as inert gas. After the addition of aqueous 1 M NaOH (40 ml) and stirring for 20 minutes, CH₂Cl₂ (50 ml) was added and the aqueous phase extracted with CH₂Cl₂ (3×20 ml). The combined organic phases were dried over Na₂SO₄. After filtration and removal of the solvent, purification was performed by means of column chromatography and the product 2-(3-chloro-benzoylamino)-7,8-dihydro-5H-pyrido[4,3-d]pyrimidine-6-carboxylic acid tert-butyl ester 790 mg (2.55 mmol, 53% of theoretical) was obtained.

b) Production of 3-chloro-N-[6-(2-methyl-benzoyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-benzamide

Trifluoroacetic acid 4.0 ml (54 mmol) was added to a solution of 2-(3-chloro-benzoylamino)-7,8-dihydro-5H-pyrido[4,3-d]pyrimidine-6-carboxylic acid tert-butyl ester 307 mg (0.789 mmol) in CH₂Cl₂ (8 ml) under nitrogen as inert gas and stirring was performed for 2 h at RT. After removal of the solvent, the intermediate (3-chloro-N-(5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl)-benzamide trifluoroacetate) was dissolved in CH₂Cl₂ (10 ml) and DIPEA 380 μl and 2-methylbenzoic acid 118 mg (0.868 mmol) were added. After cooling the reaction mixture to 0° C., EDCI 166 mg (0.868 mmol) and HOAt 16 mg (0.12 mmol) were added. The reaction mixture was stirred for 1 h at 0° C. and then overnight at RT. After removal of the solvent, purification was performed by means of column chromatography and the product 3-chloro-N-[6-(2-methyl-benzoyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-benzamide 260 mg (0.64 mmol, 81% of theoretical) was obtained.

Example 121 4-Ethyl-N-[6-(thiophene-3-sulfonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-benzamide a) Production of 2-(4-ethyl-benzoylamino)-7,8-dihydro-5H-pyrido[4,3-d]pyrimidine-6-carboxylic Acid tert-butyl Ester

2-Amino-7,8-dihydro-5H-pyrido[4,3-d]pyrimidine-6-carboxylic acid tert-butyl ester 501 mg (2.0 mmol) was added at 0° C. to a solution of 4-ethylbenzoic acid chloride 296 μl (2.0 mmol) in pyridine (25 ml) and stirring was performed for 2 h at 0° C. and then overnight at RT under nitrogen as inert gas. After the addition of aqueous 1 M NaOH (40 ml) and stirring for 20 minutes, CH₂Cl₂ (50 ml) was added and the aqueous phase extracted with CH₂Cl₂ (3×20 ml). The combined organic phases were dried over Na₂SO₄. After filtration and removal of the solvent, purification was performed by means of column chromatography and the product 2-(4-ethyl-benzoylamino)-7,8-dihydro-5H-pyrido[4,3-d]pyrimidine-6-carboxylic acid tert-butyl ester 640 mg (1.67 mmol, 84% of theoretical) was obtained.

b) Production of 4-ethyl-N-[6-(thiophene-3-sulfonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-benzamide

Trifluoroacetic acid 7.3 ml (96 mmol) was added to a solution of 2-(4-ethyl-benzoylamino)-7,8-dihydro-5H-pyrido[4,3-d]pyrimidine-6-carboxylic acid tert-butyl ester 567 mg (1.48 mmol) in CH₂Cl₂ (10 ml) under nitrogen as inert gas and stirring was performed for 1.5 h at RT. After removal of the solvent, the intermediate (4-ethyl-N-(5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl)-benzamide trifluoroacetate) was dissolved in CH₂Cl₂ (10 ml). After the addition of triethylamine 1150 μl (8.20 mmol), the solution was cooled to 0° C. and 3-thiophene sulfonyl chloride 253 mg (1.39 mmol) was added. The reaction mixture was stirred for 1 h at 0° C. and then overnight at RT. After removal of the solvent, purification was performed by means of column chromatography and the product 4-ethyl-N-[6-(thiophene-3-sulfonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-benzamide 400 mg (0.93 mmol, 63% of theoretical) was obtained.

Example 125 N-[6-(3-bromo-benzenesulfonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-3-chloro-benzamide a) Production of 2-(3-chloro-benzoylamino)-7,8-dihydro-5H-pyrido[4,3-d]pyrimidine-6-carboxylic Acid tert-butyl Ester

2-Amino-7,8-dihydro-5H-pyrido[4,3-d]pyrimidine-6-carboxylic acid tert-butyl ester 1202 mg (4.8 mmol) was added at 0° C. to a solution of 3-chlorobenzoic acid chloride 615 μl (4.8 mmol) in pyridine (25 ml) and stirring was performed for 2 h at 0° C. and then overnight at RT under nitrogen as inert gas. After the addition of aqueous 1 M NaOH (40 ml) and stirring for 20 minutes, CH₂Cl₂ (50 ml) was added and the aqueous phase extracted with CH₂Cl₂ (3×20 ml). The combined organic phases were dried over Na₂SO₄. After filtration and removal of the solvent, purification was performed by means of column chromatography and the product 2-(3-chloro-benzoylamino)-7,8-dihydro-5H-pyrido[4,3-d]pyrimidine-6-carboxylic acid tert-butyl ester 790 mg (2.55 mmol, 53% of theoretical) was obtained.

b) Production of N-[6-(3-bromo-benzenesulfonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-3-chloro-benzamide

Trifluoroacetic acid 6.2 ml (81 mmol) was added to a solution of 2-(3-chloro-benzoylamino)-7,8-dihydro-5H-pyrido[4,3-d]pyrimidine-6-carboxylic acid tert-butyl ester 487 mg (1.25 mmol) in CH₂Cl₂ (8 ml) under nitrogen as inert gas and stirring was performed for 1.5 h at RT. After removal of the solvent, the intermediate (3-chloro-N-(5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl)-benzamide trifluoroacetate) was dissolved in CH₂Cl₂ (15 ml). After the addition of triethylamine 820 μl (5.84 mmol), the solution was cooled to 0° C. and 3-bromo benzenesulfonyl chloride 311 mg (1.37 mmol) was added. The reaction mixture was stirred for 1 h at 0° C. and then overnight at RT. After removal of the solvent, purification was performed by means of column chromatography and the product N-[6-(3-bromo-benzenesulfonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-3-chloro-benzamide 525 mg (81% of theoretical) was obtained.

General Method for the Production of Substituted 5,6,7,8-tetrahydro-quinazolin-2-yl Compounds

The synthesis of 1,4-dioxa-spiro[4.5]dec-8-ylamine of the formula C proceeded as described in detail hereinafter.

Sulfonylation of 1,4-dioxa-spiro[4.5]dec-8-ylamine of the formula C proceeded by means of sulfonyl chlorides of the general formula R⁶—S(═O)₂—Cl.

For sulfonylation, K₂CO₃ (5 equivalents) was added to a solution of 1,4-dioxa-spiro[4.5]dec-8-ylamine of the formula C (1 equivalent) in CH₃CN. A solution of the respective sulfonyl chloride (1 equivalent) in CH₃CN was added and stirring was performed at RT for 2 h under nitrogen as inert gas. The reaction mixture was filtered and the residue washed with CH₂Cl₂. After purification by column chromatography, the respective compound of the general formula D was obtained.

Alternatively, for sulfonylation, triethylamine (2 equivalents) and the respective sulfonyl chloride (1 equivalent) were added at 0° C. to a solution of 1,4-dioxa-spiro[4.5]dec-8-ylamine of the formula C (1 equivalent) in CH₂Cl₂. The reaction mixture was stirred overnight at RT. The respective compound of the general formula D was obtained after removal of the solvent and purification by means of preparative HPLC or column chromatography.

Acylation of the compounds C proceeded with carboxylic acid chlorides of the general formula R⁵—C(═O)—Cl, carboxylic acid bromides of the general formula R⁵—C(═O)—Br or by reaction with carboxylic acids of the general formula R⁵—C(═O)—OH.

For acylation by means of a carboxylic acid, the compound C (1 equivalent) was dissolved in CH₂Cl₂ and DIPEA and the respective carboxylic acid (1 equivalent) were added. After cooling of the reaction mixture to 0° C., EDCI (1 equivalent) and HOAt (0.15 equivalents) were added. The reaction mixture was stirred for 1 h at 0° C. and then overnight at RT. After removal of the solvent, the respective compound of the formula D was purified by means of column chromatography.

For acylation by means of a carboxylic acid halide, the respective compound of the general formula D (1 equivalent) was dissolved in CH₂Cl₂, triethylamine (2 equivalents), a catalytic quantity of DMAP and the respective carboxylic acid halide (1 equivalent) were added and then stirring was performed overnight at RT. After removal of the solvent and purification by means of column chromatography, the respective compound of the general formula D was obtained.

Reaction to yield the compounds of the formulae D to I proceeded as described in detail hereinafter.

Reaction of the respective compound I to yield the compounds J proceeded by acylation with carboxylic acid chlorides of the general formula R³—(C═O)—Cl, carboxylic acid bromides of the general formula R³—(C═O)—Br or by reaction with carboxylic acids of the general formula R³—(C═O)—OH.

For acylation by means of a carboxylic acid, the respective compound I (1 equivalent) was dissolved in CH₂Cl₂ and DIPEA and the respective carboxylic acid (1 equivalent) were added. After cooling of the reaction mixture to 0° C., EDCI (1 equivalent) and HOAt (0.15 equivalents) were added. The reaction mixture was stirred for 1 h at 0° C. and then overnight at RT. After removal of the solvent, the respective compound of the general formula J was purified by means of column chromatography.

For acylation by means of a carboxylic acid halide, the respective compound of the general formula I (1 equivalent) was dissolved in CH₂Cl₂, triethylamine (2 equivalents), a catalytic quantity of DMAP and the respective carboxylic acid halide (1 equivalent) were added and then stirring was performed overnight at RT. After removal of the solvent and purification by means of column chromatography, the respective compound of the general formula J was obtained.

Final elimination of the BOC protective group proceeded as described in detail hereinafter.

Example 180 Thiophene-2-carboxylic acid [6-(2,5-dichloro-thiophene-3-sulfonylamino)-5,6,7,8-tetrahydro-quinazolin-2-yl]-amide a) Production of benzyl-(1,4-dioxa-spiro[4.5]dec-8-yl)-amine

Na(OAc)₃BH 2.03 g (9.6 mmol) was added to a solution of 1,4-dioxa-spiro[4.5]decan-8-one 1.0 g (6.4 mmol) and benzylamine 0.69 g (6.4 mmol) in CH₂Cl₂ (20 ml) under nitrogen as inert gas and stirring was performed for 2 h at RT. After the addition of CH₂Cl₂ (80 ml), the organic phase was washed with aqueous saturated NaHCO₃ solution. After drying of the separated organic phases over Na₂SO₄ and filtration, the solvent was removed by distillation and the product benzyl-(1,4-dioxa-spiro[4.5]dec-8-yl)-amine 1.6 g (100% of theoretical) was obtained.

b) Production of 1,4-dioxa-spiro[4.5]dec-8-ylamine

Benzyl-(1,4-dioxa-spiro[4.5]dec-8-yl)-amine (6.4 mmol) was dissolved in EtOH (10 ml) and hydrogenated under nitrogen with Pd(C) 340 mg (0.32 mmol) with stirring overnight at RT. The reaction mixture was filtered out over Celite and washed with CH₂Cl₂. After removal of the solvent, the product 1,4-dioxa-spiro[4.5]dec-8-ylamine 824 mg (82% of theoretical) was obtained.

c) Production of 2,5-dichloro-thiophene-3-sulfonic acid (1,4-dioxa-spiro[4.5]dec-8-yl)-amide

K₂CO₃ 2.51 g (18.16 mmol) was added to a solution of 1,4-dioxa-spiro[4.5]dec-8-ylamine 571 mg (3.63 mmol) in CH₃CN (10 ml). A solution of 3,5-dichlorothiophene-3-sulfonylchloride (914 mg, 3.63 mmol) in CH₃CN (10 ml) was added and stirring was performed at RT for 100 min under nitrogen as inert gas. The reaction mixture was filtered and the residue washed with CH₂Cl₂. After purification by column chromatography, the 2,5-dichloro-thiophene-3-sulfonic acid (1,4-dioxa-spiro[4.5]dec-8-yl)-amide 914 mg (68% of theoretical) was obtained.

d) Production of 2,5-dichloro-thiophene-3-sulfonic Acid (4-oxo-cyclohexyl)-amide

p-TosOH×H₂O 4 g (21.0 mmol) was added to a solution of 2,5-dichloro-thiophene-3-sulfonic acid-(1,4-dioxa-spiro[4.5]dec-8-yl)-amide 894 mg (2.40 mmol) in acetone (10 ml) and water (1 ml) and stirring was performed for 6 h at RT. After addition of aqueous 1M NaOH (100 ml) and aqueous saturated NaCl solution (100 ml), extraction was performed with CH₂Cl₂ (3×200 ml). After separation of the organic phases, drying over Na₂SO₄ and filtration, the solvent was removed by distillation. After purification by means of column chromatography, the product 2,5-dichloro-thiophene-3-sulfonic acid (4-oxo-cyclohexyl)-amide 634 mg (80% of theoretical) was obtained.

e) Production of N-Boc-Protected 2,5-dichloro-thiophene-3-sulfonic Acid (4-oxo-cyclohexyl)-amide

Et₃N 179 mg (1.77 mmol) and DMAP 29 mg (0.24 mmol) were added to a solution of 2,5-dichloro-thiophene-3-sulfonic acid (4-oxo-cyclohexyl)-amide 388 mg (1.18 mmol) in CH₂Cl₂ (10 ml). After cooling to 0° C., Boc₂O 386 mg (1.77 mmol) was added and stirring was performed for 2 h under nitrogen as inert gas. After removal of the solvent and purification by means of column chromatography, the product N-Boc-protected 2,5-dichloro-thiophene-3-sulfonic acid (4-oxo-cyclohexyl)-amide 419 mg (83% of theoretical) was obtained.

f) Production of 2,5-dichloro-thiophene-3-sulfonic Acid (2-amino-5,6,7,8-tetrahydro-quinazoline-6-yl)-amide

A reaction solution of N-Boc-protected 2,5-dichloro-thiophene-3-sulfonic acid (4-oxo-cyclohexyl)-amide 383 mg (0.89 mmol) and dimethoxymethyl-dimethyl-amine 533 mg (4.47 mmol) in toluene (10 ml) was refluxed for 4 h with stirring and nitrogen as inert gas. After removal of the solvent, the crude product N-Boc-protected 2,5-dichloro-thiophene-3-sulfonic acid (3-dimethylamino-methylene-4-oxo-cyclohexyl)-amide was obtained, which was used without further purification in the next step.

Guanidine hydrochloride 245 mg (2.56 mmol) was added to a solution of sodium 59 mg (2.6 mmol) in absolute ethanol (26 ml) and stirring was performed for 30 min at RT under nitrogen as inert gas. 9 ml (60 mmol) of this reaction mixture was added to N-Boc-protected 2,5-dichloro-thiophene-3-sulfonic acid (3-dimethylaminomethylene-4-oxo-cyclohexyl)-amide (0.89 mmol) and refluxing was performed for 8 h under nitrogen as inert gas. After the addition of CH₂Cl₂ (5 ml) and TFA (5 ml) and stirring for 1 h at RT and removal of the solvent, purification was performed by means of column chromatography and the product 2,5-dichloro-thiophene-3-sulfonic acid (2-amino-5,6,7,8-tetrahydro-quinazolin-6-yl)-amide 133 mg (39% of theoretical) was obtained.

g) Production of N-Boc-Protected 2,5-dichloro-thiophene-3-sulfonic Acid (2-amino-5,6,7,8-tetrahydro-quinazolin-6-yl)-amide

Boc₂O 41 mg (0.188 mmol) and DMAP 2 mg (0.016 mmol) was added at 0° C. to a solution of 2,5-dichloro-thiophene-3-sulfonic acid (2-amino-5,6,7,8-tetrahydro-quinazolin-6-yl)-amide 63 mg (0.17 mmol) in CH₂Cl₂ (10 ml) and stirring was performed under nitrogen as inert gas for 3.5 h at 0° C. After the addition of Boc₂O 20 mg and stirring for 30 min at 0° C., the solvent was removed by distillation. After purification by means of column chromatography, the product N-Boc-protected 2,5-dichloro-thiophene-3-sulfonic acid (2-amino-5,6,7,8-tetrahydro-quinazolin-6-yl)-amide 58 mg (73% of theoretical) was obtained.

h) Production of N-Boc-Protected thiophene-2-carboxylic Acid [6-(2,5-dichloro-thiophene-3-sulfonylamino)-5,6,7,8-tetrahydro-quinazolin-2-yl]-amide

Thiophene-2-carboxylic acid chloride 25 mg (0.17 mmol) dissolved in (1 ml) was added at 0° C. to a solution of N-Boc-protected 2,5-dichloro-thiophene-3-sulfonic acid (2-amino-5,6,7,8-tetrahydro-quinazolin-6-yl)-amide 54 mg (0.11 mmol) in CH₂Cl₂ (4 ml) and pyridine (5 ml) and stirring was performed for 1 h at 0° C. and overnight at RT and under nitrogen as inert gas. After removal of the solvent and purification by means of column chromatography, the product N-Boc-protected thiophene-2-carboxylic acid [6-(2,5-dichloro-thiophene-3-sulfonylamino)-5,6,7,8-tetrahydro-quinazolin-2-yl]-amide 21 mg (32% of theoretical) was obtained.

i) Production of thiophene-2-carboxylic Acid [6-(2,5-dichloro-thiophene-3-sulfonylamino)-5,6,7,8-tetrahydro-quinazolin-2-yl]-amide

TFA (2 ml) was added to a solution of N-Boc-protected thiophene-2-carboxylic acid [6-(2,5-dichloro-thiophene-3-sulfonylamino)-5,6,7,8-tetrahydro-quinazolin-2-yl]-amide 21 mg (36 μmol) in CH₂Cl₂ (1 ml) and stirring was performed for 2 h at RT. After removal of the solvent and purification by means of column chromatography, the product thiophene-2-carboxylic acid [6-(2,5-dichloro-thiophene-3-sulfonylamino)-5,6,7,8-tetrahydro-quinazolin-2-yl]-amide 12 mg (69% of theoretical) was obtained.

The production, not described in detail above, of the other compounds according to the Examples stated below also proceeded in accordance with the above-stated production methods, wherein the educts used in each case are known to the person skilled in the art on the basis of these methods.

Example Compound 1 3-fluoro-N-[6-(4-fluoro-benzoyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2- yl]-benzamide 2 3,5-dichloro-N-[6-(3-fluoro-4-methoxy-benzoyl)-5,6,7,8-tetrahydro- pyrido[4,3-d]pyrimidin-2-yl]-benzamide 3 4-tert-butyl-N-(6-hexanoyl-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl)- benzamide 4 N-(6-acetyl-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl)-3,4-dichloro- benzamide 5 3,5-dichloro-N-[6-(3-trifluoromethyl-benzoyl)-5,6,7,8-tetrahydro- pyrido[4,3-d]pyrimidin-2-yl]-benzamide 6 3-chloro-N-[6-(4-methoxy-2,3,6-trimethyl-benzenesulfonyl)-5,6,7,8-tetrahydro- pyrido[4,3-d]pyrimidin-2-yl]-benzamide 7 N-[6-(2-ethoxy-benzoyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-3- fluoro-benzamide 8 3-chloro-N-[6-(3-phenyl-propionyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin- 2-yl]-benzamide 9 4-tert-butyl-N-[6-(isoxazole-5-carbonyl)-5,6,7,8-tetrahydro- pyrido[4,3-d]pyrimidin-2-yl]-benzamide 10 N-[6-(2-benzylsulfanyl-acetyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]- 2-methoxy-benzamide 11 thiophene-2-carboxylic acid {6-[2-(4-chloro-phenyl)-2-methyl-propionyl]- 5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl}-amide 12 N-(6-benzoyl-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl)-3-methyl- benzamide 13 N-[6-(2,3-dihydro-benzofuran-5-carbonyl)-5,6,7,8-tetrahydro- pyrido[4,3-d]pyrimidin-2-yl]-2-fluoro-benzamide 14 thiophene-2-carboxylic acid [6-(3,4,5-trimethoxy-benzoylamino)-5,6,7,8- tetrahydro-quinazolin-2-yl]-amide 15 naphthalene-1-carboxylic acid [6-(3-methyl-5-phenyl-isoxazole-4-carbonyl)- 5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-amide 16 3-chloro-N-{6-[2-(5-methyl-2-phenyl-thiazol-4-yl)-acetyl]-5,6,7,8-tetrahydro- pyrido[4,3-d]pyrimidin-2-yl}-benzamide 17 N-[6-(4-chloro-2,5-dimethyl-benzenesulfonyl)-5,6,7,8-tetrahydro- pyrido[4,3-d]pyrimidin-2-yl]-2-trifluoromethyl-benzamide 18 N-[6-(1-benzenesulfonyl-1H-indole-2-carbonyl)-5,6,7,8-tetrahydro- pyrido[4,3-d]pyrimidin-2-yl]-3-methoxy-benzamide 20 N-[6-(5-methyl-1-phenyl-1H-pyrazole-4-sulfonyl)-5,6,7,8-tetrahydro- pyrido[4,3-d]pyrimidin-2-yl]-2-trifluoromethyl-benzamide 21 N-[6-(3-chloro-2-methyl-benzenesulfonyl)-5,6,7,8-tetrahydro- pyrido[4,3-(d)]pyrimidin-2-yl]-3-fluoro-benzamide 22 3,5-dichloro-N-[6-(3,5-dimethyl-isoxazole-4-carbonyl)-5,6,7,8-tetrahydro- pyrido[4,3-d]pyrimidin-2-yl]-benzamide 23 thiophene-2-carboxylic acid [6-(4-trifluoromethoxy-benzenesulfonylamino)- 5,6,7,8-tetrahydro-quinazolin-2-yl]-amide 25 N-[6-(furan-2-carbonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-3- methoxy-benzamide 26 N-{6-[4-(2,3-dihydro-indol-1-yl)-4-oxo-butyryl]-5,6,7,8-tetrahydro- pyrido[4,3-d]pyrimidin-2-yl}-3-methyl-benzamide 27 N-{6-[2-(4-methyl-cyclohexyl)-acetyl]-5,6,7,8-tetrahydro- pyrido[4,3-d]pyrimidin-2-yl}-2-trifluoromethyl-benzamide 28 3,4-difluoro-N-[6-(6-phenoxy-pyridine-3-carbonyl)-5,6,7,8-tetrahydro- pyrido[4,3-d]pyrimidin-2-yl]-benzamide 29 4-tert-butyl-N-[6-(2-phenyl-thiazole-4-carbonyl)-5,6,7,8-tetrahydro- pyrido[4,3-d]pyrimidin-2-yl]-benzamide 30 3,5-dichloro-N-[6-(2-trifluoromethyl-benzenesulfonyl)-5,6,7,8-tetrahydro- pyrido[4,3-d]pyrimidin-2-yl]-benzamide 31 thiophene-2-carboxylic acid [6-(3-bromo-benzenesulfonylamino)-5,6,7,8- tetrahydro-quinazolin-2-yl]-amide 32 N-[6-(2-chloro-pyridine-4-carbonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin- 2-yl]-3-methoxy-benzamide 33 4-fluoro-N-[6-(2-methanesulfonyl-benzenesulfonylamino)-5,6,7,8-tetrahydro- quinazolin-2-yl]-benzamide 35 N-(6-dimethylsulfamoyl-5,6,7,8-tetrahydro-pyrido[4,3-(d)]pyrimidin-2-yl)-3- fluoro-benzamide 36 3-fluoro-N-{6-[2-(4-trifluoromethyl-phenyl)-acetyl]-5,6,7,8-tetrahydro- pyrido[4,3-(d)]pyrimidin-2-yl}-benzamide 37 N-{6-[2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-acetyl]-5,6,7,8-tetrahydro- pyrido[4,3-(d)]pyrimidin-2-yl}-2-trifluoromethyl-benzamide 38 thiophene-2-carboxylic acid {6-[4-(4-chloro-2-methyl-phenoxy)-butyrylamino]- 5,6,7,8-tetrahydro-quinazolin-2-yl}-amide 39 N-[6-(butane-1-sulfonyl)-5,6,7,8-tetrahydro-pyrido[4,3-(d)]pyrimidin-2-yl]-3- fluoro-benzamide 40 2-methoxy-N-[6-(2-propyl-pentanoyl)-5,6,7,8-tetrahydro- pyrido[4,3-d]pyrimidin-2-yl]-benzamide 41 N-[6-(4,5-dichloro-thiophene-2-sulfonylamino)-5,6,7,8-tetrahydro-quinazolin- 2-yl]-4-fluoro-benzamide 42 4-chloro-N-[6-(2-trifluoromethyl-benzenesulfonyl)-5,6,7,8-tetrahydro- pyrido[4,3-d]pyrimidin-2-yl]-benzamide 43 thiophene-2-carboxylic acid [6-(4-methoxy-benzenesulfonylamino)-5,6,7,8- tetrahydro-quinazolin-2-yl]-amide 44 5-[2-(3,4-difluoro-benzoylamino)-7,8-dihydro-5H-pyrido[4,3-(d)]pyrimidin-6- yl]-5-oxo-valeric acid methyl ester 45 N-[6-(benzo[b]thiophene-3-carbonyl)-5,6,7,8-tetrahydro- pyrido[4,3-d]pyrimidin-2-yl]-4-chloro-benzamide 46 N-[6-(5-bromo-2-methoxy-benzenesulfonylamino)-5,6,7,8-tetrahydro- quinazolin-2-yl]-4-fluoro-benzamide 47 4-fluoro-N-[6-(4-fluoro-benzenesulfonylamino)-5,6,7,8-tetrahydro-quinazolin- 2-yl]-benzamide 48 N-{6-[2-(1H-indol-3-yl)-2-oxo-acetyl]-5,6,7,8-tetrahydro- pyrido[4,3-d]pyrimidin-2-yl}-2-trifluoromethyl-benzamide 49 5-tert-butyl-2-methyl-furan-3-carboxylic acid {2-[(thiophene-2-carbonyl)- amino]-5,6,7,8-tetrahydro-quinazolin-6-yl}-amide 50 N-[6-(2,5-dimethoxy-benzenesulfonyl)-5,6,7,8-tetrahydro- pyrido[4,3-d]pyrimidin-2-yl]-3-methoxy-benzamide 51 benzoic acid 2-{2-[(thiophene-2-carbonyl)-amino]-5,6,7,8-tetrahydro- quinazolin-6-ylcarbamoyl}-benzyl ester 52 3,4-difluoro-N-(6-hexanoyl-5,6,7,8-tetrahydro-pyrido[4,3-(d)]pyrimidin-2-yl)- benzamide 53 4-ethyl-N-[6-(tetrahydro-furan-2-carbonyl)-5,6,7,8-tetrahydro- pyrido[4,3-d]pyrimidin-2-yl]-benzamide 54 N-[6-(2-chloro-benzenesulfonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2- yl]-3-fluoro-benzamide 55 4-tert-butyl-N-[6-(5-tert-butyl-2-methyl-2H-pyrazole-3-carbonyl)-5,6,7,8- tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-benzamide 56 3-methoxy-N-[6-(4-methoxy-benzenesulfonyl)-5,6,7,8-tetrahydro- pyrido[4,3-d]pyrimidin-2-yl]-benzamide 57 {2-[2-(3,4-difluoro-benzoylamino)-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-6- yl]-2-oxo-1-phenyl-ethyl}-carbamic acid benzyl ester 58 5-phenyl-oxazole-4-carboxylic acid {2-[(thiophene-2-carbonyl)-amino]-5,6,7,8- tetrahydro-quinazolin-6-yl}-amide 59 4-chloro-N-(6-dimethylsulfamoyl-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2- yl)-benzamide 60 4-tert-butyl-N-[6-(2-fluoro-benzenesulfonyl)-5,6,7,8-tetrahydro- pyrido[4,3-d]pyrimidin-2-yl]-benzamide 61 4-chloro-N-[6-(3-cyclopentyl-propionyl)-5,6,7,8-tetrahydro- pyrido[4,3-d]pyrimidin-2-yl]-benzamide 62 4-chloro-N-[6-(4-phenyl-butyryl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2- yl]-benzamide 63 4-tert-butyl-N-[6-(5-methyl-2-phenyl-2H-[1,2,3]triazole-4-carbonyl)-5,6,7,8- tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-benzamide 64 2-chloro-N-{2-[(thiophene-2-carbonyl)-amino]-5,6,7,8-tetrahydro-quinazolin-6- yl}-isonicotinamide 66 N-[6-(5-chloro-thiophene-2-sulfonyl)-5,6,7,8-tetrahydro- pyrido[4,3-d]pyrimidin-2-yl]-3-fluoro-benzamide 67 N-[6-(4-diethylamino-benzoyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2- yl]-3-methoxy-benzamide 68 N-[6-(2,4-dimethyl-thiazole-5-sulfonyl)-5,6,7,8-tetrahydro- pyrido[4,3-d]pyrimidin-2-yl]-3-methyl-benzamide 69 4-chloro-N-[6-naphthalene-2-carbonyl)-5,6,7,8-tetrahydro- pyrido[4,3-d]pyrimidin-2-yl]-benzamide 70 N-[6-(2,4-difluoro-benzenesulfonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin- 2-yl]-2-methoxy-benzamide 71 3,4-dichloro-N-[6-(4-chloro-benzenesulfonyl)-5,6,7,8-tetrahydro- pyrido[4,3-d]pyrimidin-2-yl]-benzamide 72 3,4-difluoro-N-[6-(thiophene-2-sulfonyl)-5,6,7,8-tetrahydro- pyrido[4,3-d]pyrimidin-2-yl]-benzamide 74 4-ethyl-N-[6-(4-pyrazol-1-yl-benzoyl)-5,6,7,8-tetrahydro- pyrido[4,3-d]pyrimidin-2-yl]-benzamide 75 N-[6-(7,7-dimethyl-2-oxo-bicyclo[2.2.1]hept-1-ylmethanesulfonylamino)- 5,6,7,8-tetrahydro-quinazolin-2-yl]-butyramide 76 5-oxo-5-phenyl-valeric acid (2-butyrylamino-5,6,7,8-tetrahydro-quinazolin-6- yl)-amide 77 3-[2-(4-chloro-benzoylamino)-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-6-yl]-3- oxo-propionic acid methyl ester 78 N-{6-[5-(4-chloro-phenyl)-2-methyl-furan-3-carbonyl]-5,6,7,8-tetrahydro- pyrido[4,3-d]pyrimidin-2-yl}-2-methoxy-benzamide 79 4-chloro-N-[6-(2,4-dimethyl-thiazole-5-sulfonyl)-5,6,7,8-tetrahydro- pyrido[4,3-d]pyrimidin-2-yl]-benzamide 80 N-[6-(2,3-difluoro-benzoyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-3- methoxy-benzamide 81 4-chloro-N-{6-[2-(2-methoxy-ethoxy)-acetyl]-5,6,7,8-tetrahydro- pyrido[4,3-d]pyrimidin-2-yl}-benzamide 82 2-[2-(2-ethoxy-benzoylamino)-7,8-dihydro-5H-pyrido[4,3-d]pyrimidine-6- sulfonyl]-benzoic acid methyl ester 83 4-tert-butyl-N-[6-(4-nitro-benzenesulfonyl)-5,6,7,8-tetrahydro- pyrido[4,3-d]pyrimidin-2-yl]-benzamide 86 N-[6-(5-chloro-thiophene-2-sulfonyl)-5,6,7,8-tetrahydro- pyrido[4,3-d]pyrimidin-2-yl]-2-methoxy-benzamide 87 4-fluoro-N-[6-(furan-2-carbonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2- yl]-benzamide 88 4-{2-[(thiophene-2-carbonyl)-amino]-5,6,7,8-tetrahydro-quinazolin-6- ylcarbamoyl}-piperidine-1-carboxylic acid tert-butyl ester 89 1-(4-chloro-phenyl)-cyclopropanecarboxylic acid (2-butyrylamino-5,6,7,8- tetrahydro-quinazolin-6-yl)-amide 90 N-(6-ethanesulfonyl-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl)-3- methoxy-benzamide 91 5-methyl-thiophene-2-carboxylic acid (2-butyrylamino-5,6,7,8-tetrahydro- quinazolin-6-yl)-amide 92 4-tert-butyl-N-[6-(4-methyl-3-nitro-benzoyl)-5,6,7,8-tetrahydro- pyrido[4,3-d]pyrimidin-2-yl]-benzamide 94 4-fluoro-N-[6-(3-phenyl-propionylamino)-5,6,7,8-tetrahydro-quinazolin-2-yl]- benzamide 95 3,4-dichloro-N-[6-(2,4,6-trimethyl-benzenesulfonyl)-5,6,7,8-tetrahydro- pyrido[4,3-d]pyrimidin-2-yl]-benzamide 96 N-[6-(4-methyl-3,4-dihydro-2H-benzo[1,4]oxazine-7-sulfonyl)-5,6,7,8- tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-nicotinamide 97 thiophene-2-carboxylic acid [6-(3,5-difluoro-benzoylamino)-5,6,7,8-tetrahydro- quinazolin-2-yl]-amide 98 N-[6-(2,4-difluoro-benzenesulfonylamino)-5,6,7,8-tetrahydro-quinazolin-2-yl]- butyramide 99 thiophene-2-carboxylic acid [6-(2,3,5,6-tetramethyl-benzenesulfonyl)-5,6,7,8- tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-amide 101 N-[6-(3,4-dichloro-benzoyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-4- ethyl-benzamide 102 N-[6-(7,7-dimethyl-2-oxo-bicyclo[2.2.1]hept-1-ylmethanesulfonyl)-5,6,7,8- tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-3-fluoro-benzamide 103 N-[6-(6-fluoro-4H-benzo[1,3]dioxin-8-carbonyl)-5,6,7,8-tetrahydro- pyrido[4,3-d]pyrimidin-2-yl]-2-trifluoromethyl-benzamide 104 [5-(2-butyrylamino-5,6,7,8-tetrahydro-quinazolin-6-ylcarbamoyl)-pentyl]- carbamic acid benzyl ester 105 2-ethoxy-N-[6-(4-oxo-pentanoyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2- yl]-benzamide 106 naphthalene-1-carboxylic acid [6-(propane-1-sulfonyl)-5,6,7,8-tetrahydro- pyrido[4,3-d]pyrimidin-2-yl]-amide 107 N-[6-(5-fluoro-2-methyl-benzenesulfonyl)-5,6,7,8-tetrahydro- pyrido[4,3-d]pyrimidin-2-yl]-4-methyl-benzamide 109 3-chloro-N-[6-(2-methyl-benzoyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2- yl]-benzamide 110 thiophene-2-carboxylic acid [6-(3-chloro-benzo[b]thiophene-2-carbonyl)- 5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-amide 112 thiophene-2-carboxylic acid [6-(2-cyclopentyl-acetylamino)-5,6,7,8-tetrahydro- quinazolin-2-yl]-amide 113 N-[6-(3,4-dichloro-benzoyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-2- fluoro-benzamide 114 N-[6-(2-chloro-benzenesulfonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2- yl]-4-ethyl-benzamide 115 thiophene-2-carboxylic acid [6-(4-bromo-3-methyl-benzoylamino)-5,6,7,8- tetrahydro-quinazolin-2-yl]-amide 116 3-methyl-N-[6-(toluene-3-sulfonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin- 2-yl]-benzamide 117 naphthalene-1-carboxylic acid [6-(5-chloro-thiophene-2-sulfonyl)-5,6,7,8- tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-amide 118 N-(2-butyrylamino-5,6,7,8-tetrahydro-quinazolin-6-yl)-2,6-difluoro-benzamide 119 3-chloro-N-[6-(3,4-dimethoxy-benzoyl)-5,6,7,8-tetrahydro- pyrido[4,3-d]pyrimidin-2-yl]-benzamide 120 N-[6-(3-chloro-benzo[b]thiophene-2-carbonyl)-5,6,7,8-tetrahydro- pyrido[4,3-d]pyrimidin-2-yl]-benzamide 121 4-ethyl-N-[6-(thiophene-3-sulfonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin- 2-yl]-benzamide 123 2-ethoxy-N-[6-(2-ethylsulfanyl-pyridine-3-carbonyl)-5,6,7,8-tetrahydro- pyrido[4,3-d]pyrimidin-2-yl]-benzamide 124 3-[2-(3-chloro-benzoylamino)-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-6-yl]-3- oxo-propionic acid ethyl ester 125 N-[6-(3-bromo-benzenesulfonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2- yl]-3-chloro-benzamide 126 3,4-dichloro-N-{6-[2-(4-chloro-phenyl)-acetyl]-5,6,7,8-tetrahydro- pyrido[4,3-d]pyrimidin-2-yl}-benzamide 127 3-chloro-N-[6-(2-chloro-6-fluoro-benzoyl)-5,6,7,8-tetrahydro- pyrido[4,3-d]pyrimidin-2-yl]-benzamide 128 4-fluoro-N-(6-hexanoylamino-5,6,7,8-tetrahydro-quinazolin-2-yl)-benzamide 129 N-[6-(5-bromo-2-methoxy-benzenesulfonyl)-5,6,7,8-tetrahydro- pyrido[4,3-d]pyrimidin-2-yl]-3-methoxy-benzamide 132 N-[6-(3-cyclopentyl-propionyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2- yl]-isonicotinamide 133 5-benzyl-furan-2-carboxylic acid (2-butyrylamino-5,6,7,8-tetrahydro- quinazolin-6-yl)-amide 134 3,4-dichloro-N-[6-(4-trifluoromethoxy-benzenesulfonyl)-5,6,7,8-tetrahydro- pyrido[4,3-d]pyrimidin-2-yl]-benzamide 135 [(2-butyrylamino-5,6,7,8-tetrahydro-quinazolin-6-ylcarbamoyl)-phenyl- methyl]-carbamic acid benzyl ester 136 N-[6-(3,4-dimethoxy-benzenesulfonyl)-5,6,7,8-tetrahydro- pyrido[4,3-d]pyrimidin-2-yl]-4-fluoro-benzamide 137 2-fluoro-N-[6-(2-methyl-5-phenyl-furan-3-carbonyl)-5,6,7,8-tetrahydro- pyrido[4,3-d]pyrimidin-2-yl]-benzamide 138 thiophene-2-carboxylic acid (6-pent-4-enoylamino-5,6,7,8-tetrahydro- quinazolin-2-yl)-amide 139 (2-methyl-1-{2-[(thiophene-2-carbonyl)-amino]-5,6,7,8-tetrahydro-quinazolin- 6-ylcarbamoyl}-propyl)-carbamic acid 9H-fluoren-9-ylmethyl ester 140 (5-{2-[(thiophene-2-carbonyl)-amino]-5,6,7,8-tetrahydro-quinazolin-6- ylcarbamoyl}-pentyl)-carbamic acid tert-butyl ester 141 3-fluoro-N-[6-(1,2,3,4-tetrahydro-naphthalene-2-carbonyl)-5,6,7,8-tetrahydro- pyrido[4,3-d]pyrimidin-2-yl]-benzamide 142 4-chloro-N-{6-[2-(2,5-dioxo-imidazolidin-4-yl)-acetyl]-5,6,7,8-tetrahydro- pyrido[4,3-d]pyrimidin-2-yl}-benzamide 143 3-fluoro-N-[6-(toluene-4-sulfonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2- yl]-benzamide 144 3,5-dichloro-N-[6-(4-thiophen-2-yl-benzoyl)-5,6,7,8-tetrahydro- pyrido[4,3-d]pyrimidin-2-yl]-benzamide 145 N-[6-(3-chloro-thiophene-2-carbonyl)-5,6,7,8-tetrahydro- pyrido[4,3-d]pyrimidin-2-yl]-2-ethoxy-benzamide 146 N-[6-(toluene-3-sulfonylamino)-5,6,7,8-tetrahydro-quinazolin-2-yl]- butyramide 147 thiophene-2-carboxylic acid {6-[2-(2,2,2-trifluoro-acetyl)-1,2,3,4-tetrahydro- isoquinoline-7-sulfonylamino]-5,6,7,8-tetrahydro-quinazolin-2-yl}-amide 148 4-methyl-N-[6-(4-trifluoromethylsulfanyl-benzoyl)-5,6,7,8-tetrahydro- pyrido[4,3-d]pyrimidin-2-yl]-benzamide 149 (2-{2-[(thiophene-2-carbonyl)-amino]-5,6,7,8-tetrahydro-quinazolin-6- ylcarbamoyl}-ethyl)-carbamic acid tert-butyl ester 150 2-fluoro-N-[6-(2-methyl-5-nitro-benzenesulfonyl)-5,6,7,8-tetrahydro- pyrido[4,3-d]pyrimidin-2-yl]-benzamide 151 N-[6-(4-methoxy-benzenesulfonylamino)-5,6,7,8-tetrahydro-quinazolin-2-yl]- butyramide 152 4-chloro-N-[6-(2,4-difluoro-benzoyl)-5,6,7,8-tetrahydro- pyrido[4,3-d]pyrimidin-2-yl]-benzamide 153 4-methyl-N-(6-pent-4-enoyl-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl)- benzamide 154 naphthalene-1-carboxylic acid [6-(3-fluoro-4-methyl-benzoyl)-5,6,7,8- tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-amide 155 N-{6-[2-(4-trifluoromethyl-phenyl)-acetyl]-5,6,7,8-tetrahydro- pyrido[4,3-d]pyrimidin-2-yl}-benzamide 156 N-[6-(3,4-dichloro-benzoyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]- nicotinamide 157 4-ethyl-N-{6-[2-(2,2,2-trifluoro-acetyl)-1,2,3,4-tetrahydro-isoquinoline-7- sulfonyl]-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl}-benzamide 158 2-methoxy-N-[6-(4-methoxy-2,3,6-trimethyl-benzenesulfonyl)-5,6,7,8- tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-benzamide 159 4-ethyl-N-[6-(2-methoxy-acetyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2- yl]-benzamide 160 4-fluoro-N-[6-(propane-1-sulfonylamino)-5,6,7,8-tetrahydro-quinazolin-2-yl]- benzamide 162 N-[6-(7,7-dimethyl-2-oxo-bicyclo[2.2.1]hept-1-ylmethanesulfonylamino)- 5,6,7,8-tetrahydro-quinazolin-2-yl]-butyramide 163 N-{6-[2-(2,5-dimethyl-phenyl)-acetylamino]-5,6,7,8-tetrahydro-quinazolin-2- yl}-4-fluoro-benzamide 165 thiophene-2-carboxylic acid (6-phenylmethanesulfonylamino-5,6,7,8- tetrahydro-quinazolin-2-yl)-amide 166 N-[6-(3,4-dimethoxy-benzenesulfonylamino)-5,6,7,8-tetrahydro-quinazolin-2- yl]-butyramide 167 N-{6-[4-(1,1-dimethyl-propyl)-benzenesulfonylamino]-5,6,7,8-tetrahydro- quinazolin-2-yl}-butyramide 168 N-(2-butyrylamino-5,6,7,8-tetrahydro-quinazolin-6-yl)-3-(3-trifluoromethyl- phenyl)-acrylamide 169 N-[6-(butane-1-sulfonylamino)-5,6,7,8-tetrahydro-quinazolin-2-yl]-4-fluoro- benzamide 170 naphthalene-1-carboxylic acid (6-acetyl-5,6,7,8-tetrahydro- pyrido[4,3-d]pyrimidin-2-yl)-amide 171 3,5-dichloro-N-[6-(3-diethylcarbamoyl-propionyl)-5,6,7,8-tetrahydro- pyrido[4,3-d]pyrimidin-2-yl]-benzamide 172 4-ethyl-N-[6-(4-methoxy-benzenesulfonyl)-5,6,7,8-tetrahydro- pyrido[4,3-d]pyrimidin-2-yl]-benzamide 173 4-ethyl-N-[6-(quinoline-6-carbonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin- 2-yl]-benzamide 174 N-[6-(2-cyclopropyl-acetyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-2- fluoro-benzamide 175 N-[6-(2H-chromene-3-carbonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2- yl]-3,4-difluoro-benzamide 176 N-{6-[2-(4-chloro-phenyl)-propionyl]-5,6,7,8-tetrahydro- pyrido[4,3-d]pyrimidin-2-yl}-benzamide 177 thiophene-2-carboxylic acid [6-(2-naphthalen-1-yl-acetylamino)-5,6,7,8- tetrahydro-quinazolin-2-yl]-amide 178 4-fluoro-N-(6-phenylmethanesulfonyl-5,6,7,8-tetrahydro- pyrido[4,3-d]pyrimidin-2-yl)-benzamide 180 thiophene-2-carboxylic acid [6-(2,5-dichloro-thiophene-3-sulfonylamino)- 5,6,7,8-tetrahydro-quinazolin-2-yl]-amide 181 {5-[2-(4-fluoro-benzoylamino)-5,6,7,8-tetrahydro-quinazolin-6-ylcarbamoyl]- pentyl}-carbamic acid benzyl ester 182 N-[6-(2,5-dimethyl-2H-pyrazole-3-carbonyl)-5,6,7,8-tetrahydro- pyrido[4,3-d]pyrimidin-2-yl]-4-ethyl-benzamide 183 naphthalene-1-carboxylic acid [6-(3-fluoro-benzoyl)-5,6,7,8-tetrahydro- pyrido[4,3-d]pyrimidin-2-yl]-amide 184 N-[6-(benzo[b]thiophene-3-carbonyl)-5,6,7,8-tetrahydro- pyrido[4,3-d]pyrimidin-2-yl]-4-tert-butyl-benzamide 185 4-fluoro-N-[6-(4-methoxy-benzenesulfonyl)-5,6,7,8-tetrahydro- pyrido[4,3-d]pyrimidin-2-yl]-benzamide 186 4-tert-butyl-N-[6-(2,3-dihydro-benzo[1,4]dioxin-6-sulfonyl)-5,6,7,8-tetrahydro- pyrido[4,3-d]pyrimidin-2-yl]-benzamide 187 3-chloro-N-{6-[2-(2,6-dichloro-phenyl)-acetyl]-5,6,7,8-tetrahydro- pyrido[4,3-d]pyrimidin-2-yl}-benzamide 188 thiophene-2-carboxylic acid [6-(2,3-dihydro-benzo[1,4]dioxin-6- sulfonylamino)-5,6,7,8-tetrahydro-quinazolin-2-yl]-amide 189 N-{6-[2-(3-chloro-phenoxy)-acetyl]-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin- 2-yl}-4-methyl-benzamide 190 N-[6-(5-phenyl-pentanoyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]- benzamide 191 4-ethyl-N-[6-(2-ethyl-butyryl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]- benzamide 192 3,5-dichloro-N-[6-(4-trifluoromethoxy-benzoyl)-5,6,7,8-tetrahydro- pyrido[4,3-d]pyrimidin-2-yl]-benzamide 193 naphthalene-1-carboxylic acid [6-(4-methyl-octanoyl)-5,6,7,8-tetrahydro- pyrido[4,3-d]pyrimidin-2-yl]-amide 194 4-[2-(4-fluoro-benzoylamino)-5,6,7,8-tetrahydro-quinazolin-6-ylcarbamoyl]- piperidine-1-carboxylic acid tert-butyl ester 195 N-[6-(2-benzyloxy-acetyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-2- methoxy-benzamide 196 N-[6-(2-trifluoromethyl-benzenesulfonylamino)-5,6,7,8-tetrahydro-quinazolin- 2-yl]-butyramide 197 N-[2-(4-fluoro-benzoylamino)-5,6,7,8-tetrahydro-quinazolin-6-yl]-2-methyl-6- trifluoromethyl-nicotinamide 198 N-[6-(3-cyano-benzoyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-2- trifluoromethyl-benzamide 199 3-methoxy-N-[6-(3-trifluoromethoxy-benzoyl)-5,6,7,8-tetrahydro- pyrido[4,3-d]pyrimidin-2-yl]-benzamide 200 N-(6-butyryl-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl)-2-fluoro- benzamide 201 N-(6-benzenesulfonylamino-5,6,7,8-tetrahydro-quinazolin-2-yl)-4-fluoro- benzamide 202 N-[6-(5-chloro-thiophene-2-sulfonylamino)-5,6,7,8-tetrahydro-quinazolin-2- yl]-4-fluoro-benzamide 203 naphthalene-1-carboxylic acid (6-hexanoyl-5,6,7,8-tetrahydro- pyrido[4,3-d]pyrimidin-2-yl)-amide 204 N-(6-propionyl-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl)-2- trifluoromethyl-benzamide 205 N-[6-(2-ethyl-butyryl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-4- methyl-benzamide 206 2-fluoro-N-[6-(3-trifluoromethyl-benzenesulfonyl)-5,6,7,8-tetrahydro- pyrido[4,3-d]pyrimidin-2-yl]-benzamide 207 5-benzyl-furan-2-carboxylic acid {2-[(thiophene-2-carbonyl)-amino]-5,6,7,8- tetrahydro-quinazolin-6-yl}-amide 208 thiophene-2-carboxylic acid {6-[2-(2,5-dimethyl-phenyl)-acetylamino]-5,6,7,8- tetrahydro-quinazolin-2-yl}-amide 210 4-fluoro-N-[6-(propane-1-sulfonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin- 2-yl]-benzamide 211 2-[2-(3-fluoro-benzoylamino)-7,8-dihydro-5H-pyrido[4,3-d]pyrimidine-6- sulfonyl]-benzoic acid methyl ester 212 3,5-dichloro-N-[6-(5-[1,2]dithiolan-3-yl-pentanoyl)-5,6,7,8-tetrahydro- pyrido[4,3-d]pyrimidin-2-yl]-benzamide 213 thiophene-2-carboxylic acid [6-(2-phenoxy-butyrylamino)-5,6,7,8-tetrahydro- quinazolin-2-yl]-amide 214 thiophene-2-carboxylic acid {6-[2-(4-methoxyphenyl)-acetylamino]-5,6,7,8- tetrahydro-quinazolin-2-yl}-amide 215 N-(6-cyclohexanecarboxylic-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl)-2- trifluoromethyl-benzamide 216 N-[6-(2,4-dimethyl-thiazole-5-sulfonyl)-5,6,7,8-tetrahydro- pyrido[4,3-d]pyrimidin-2-yl]-2-trifluoromethyl-benzamide 217 2-thiophen-2-yl-thiazole-4-carboxylic acid {2-[(thiophene-2-carbonyl)-amino]- 5,6,7,8-tetrahydro-quinazolin-6-yl}-amide 219 thiophene-2-carboxylic acid {6-[3-(3-trifluoromethyl-phenyl)-acryloylamino]- 5,6,7,8-tetrahydro-quinazolin-2-yl}-amide 220 thiophene-2-carboxylic acid [6-(5-phenyl-pentanoylamino)-5,6,7,8-tetrahydro- quinazolin-2-yl]-amide 221 thiophene-2-carboxylic acid [6-(2-chloro-5-trifluoromethyl-benzoylamino)- 5,6,7,8-tetrahydro-quinazolin-2-yl]-amide 222 4-fluoro-N-[6-(2,3,5,6-tetramethyl-benzenesulfonylamino)-5,6,7,8-tetrahydro- quinazolin-2-yl]-benzamide 223 4-fluoro-N-[6-(4-methyl-octanoyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2- yl]-benzamide 224 2-{2-[(thiophene-2-carbonyl)-amino]-5,6,7,8-tetrahydro-quinazolin-6- ylsulfamoyl}-benzoic acid methyl ester 225 [(3-methyl-1-{2-[(thiophene-2-carbonyl)-amino]-5,6,7,8-tetrahydro-quinazolin- 6-ylcarbamoyl}-butylcarbamoyl)-methyl]-carbamic acid benzyl ester 226 3-chloro-N-(6-pentanoyl-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl)- benzamide 227 4-fluoro-N-[6-(5-oxo-5-phenyl-pentanoylamino)-5,6,7,8-tetrahydro-quinazolin- 2-yl]-benzamide 228 thiophene-2-carboxylic acid [6-(3-phenyl-acryloylamino)-5,6,7,8-tetrahydro- quinazolin-2-yl]-amide 229 N-[6-(5-[1,2]dithiolan-3-yl-pentanoylamino)-5,6,7,8-tetrahydro-quinazolin-2- yl]-4-fluoro-benzamide 230 benzoic acid 2-(2-{2-[(thiophene-2-carbonyl)-amino]-5,6,7,8-tetrahydro- quinazolin-6-ylcarbamoyl}-ethyl)-phenyl ester 231 4-fluoro-N-[6-(2-methyl-5-nitro-benzenesulfonylamino)-5,6,7,8-tetrahydro- quinazolin-2-yl]-benzamide 232 4-chloro-N-[6-(2-phenoxy-acetyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2- yl]-benzamide 234 N-[6-(5-bromo-thiophene-2-carbonyl)-5,6,7,8-tetrahydro- pyrido[4,3-d]pyrimidin-2-yl]-2-fluoro-benzamide 235 4-fluoro-N-[6-(5-fluoro-2-methyl-benzenesulfonylamino)-5,6,7,8-tetrahydro- quinazolin-2-yl]-benzamide 236 N-[6-(4-acetylamino-benzenesulfonylamino)-5,6,7,8-tetrahydro-quinazolin-2- yl]-4-fluoro-benzamide 237 thiophene-2-carboxylic acid [6-(2-trifluoromethyl-benzoylamino)-5,6,7,8- tetrahydro-quinazolin-2-yl]-amide 238 3,4-difluoro-N-[6-(quinoline-6-carbonyl)-5,6,7,8-tetrahydro- pyrido[4,3-d]pyrimidin-2-yl]-benzamide 239 {1-[2-(4-fluoro-benzoylamino)-5,6,7,8-tetrahydro-quinazolin-6-ylcarbamoyl]-2- phenyl-ethyl}-carbamic acid tert-butyl ester 240 thiophene-2-carboxylic acid [6-(2-methyl-benzoylamino)-5,6,7,8-tetrahydro- quinazolin-2-yl]-amide 241 3-chloro-N-{6-[3-(2-oxo-benzooxazol-3-yl)-propionyl]-5,6,7,8-tetrahydro- pyrido[4,3-d]pyrimidin-2-yl}-benzamide 242 3-chloro-N-[6-(5-chloro-thiophene-2-sulfonyl)-5,6,7,8-tetrahydro- pyrido[4,3-d]pyrimidin-2-yl]-benzamide 243 3,5-dichloro-N-[6-(4-methoxy-benzenesulfonyl)-5,6,7,8-tetrahydro- pyrido[4,3-d]pyrimidin-2-yl]-benzamide 244 4-tert-butyl-N-[6-(5-methyl-isoxazole-3-carbonyl)-5,6,7,8-tetrahydro- pyrido[4,3-d]pyrimidin-2-yl]-benzamide 245 N-[6-(5-bromo-2-methoxy-benzenesulfonyl)-5,6,7,8-tetrahydro- pyrido[4,3-d]pyrimidin-2-yl]-4-methyl-benzamide 246 4-tert-butyl-N-{6-[3-(2-hydroxyphenyl)-propionyl]-5,6,7,8-tetrahydro- pyrido[4,3-d]pyrimidin-2-yl}-benzamide 247 4-fluoro-N-[6-(2-phenyl-butyrylamino)-5,6,7,8-tetrahydro-quinazolin-2-yl]- benzamide 248 4-tert-butyl-N-[6-(4-propyl-benzoyl)-5,6,7,8-tetrahydro- pyrido[4,3-d]pyrimidin-2-yl]-benzamide 249 thiophene-2-carboxylic acid [6-(2-bromo-benzoylamino)-5,6,7,8-tetrahydro- quinazolin-2-yl]-amide 250 2-methoxy-N-[6-(6-phenoxy-pyridine-3-carbonyl)-5,6,7,8-tetrahydro- pyrido[4,3-d]pyrimidin-2-yl]-benzamide 251 N-[6-(4-acetylamino-benzenesulfonyl)-5,6,7,8-tetrahydro- pyrido[4,3-d]pyrimidin-2-yl]-4-ethyl-benzamide 252 3,5-dichloro-N-[6-(4-fluoro-benzenesulfonyl)-5,6,7,8-tetrahydro- pyrido[4,3-d]pyrimidin-2-yl]-benzamide 253 N-[6-(1-benzenesulfonyl-1H-indole-2-carbonyl)-5,6,7,8-tetrahydro- pyrido[4,3-d]pyrimidin-2-yl]-4-fluoro-benzamide 255 N-[6-(3-chloro-benzenesulfonylamino)-5,6,7,8-tetrahydro-quinazolin-2-yl]-4- fluoro-benzamide

Pharmacological Data:

The affinity of the substituted 5,6,7,8-tetrahydro-pyrido[4,3-d]-pyrimidin-2-yl or 5,6,7,8-tetrahydro-quinazolin-2-yl compound according to the invention for the batrachotoxin (BTX) binding site and for the mGluR5-receptor and the inhibition of noradrenalin or 5-HT reuptake was determined as described above.

The substituted 5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl or 5,6,7,8-tetrahydro-quinazolin-2-yl compounds according to the invention exhibit good to very good inhibition of noradrenalin reuptake and good to very good inhibition of 5-hydroxy-tryptophan reuptake.

Furthermore, these compounds according to the invention also exhibit excellent affinity for the batrachotoxin (BTX) binding site of the sodium channel and the mGluR5 receptor.

Table I below gives the respective pharmacological data for some exemplary substituted 5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl or 5,6,7,8-tetrahydro-quinazolin-2-yl compounds.

TABLE I Compound mGluR5 5-HT uptake, NA uptake, according to (MPEP), 10 μM BTX rat, 1 μM, % rat, 10 μM, Example % inhibition inhibition inhibition % inhibition 29 40.51 68 35 69 64 70 73 71 69 47 74 72 31 41 74 66 54 43 78 41.06 31 79 34 80 54 82 36.33 38 32 83 39 77 86 62 32 92 75 66 35 94 47 95 77 59 72 97 30 99 78 41 56 101 68 65 84 102 63 103 65 107 38.23 73 36 39 109 30 92 110 40 96 75 113 31.26 38 45 67 114 82 50 73 115 34.26 82 56 49 116 53 31 52 117 37 32 31 119 34 72 120 48 92 78 121 57 52 92 124 65 125 66 43 70 126 70 55 89 127 30 35 71 128 33 129 51.14 76 132 58.08 72 133 39 134 64 58 59 137 43 139 31.02 62 141 63 54 55 143 37.25 61 53 144 81 42 67 145 84.43 46 146 39.64 147 48 148 85 32 149 32 150 49 54 152 34.01 55 33 154 30.72 50 155 62 156 45.96 50 157 63 43 61 158 74 55 36 160 40 162 29 163 28 165 35 167 51 32 168 33.45 39 46 171 32 172 70.12 57 57 85 173 69 175 49 32 46 176 38 177 41.98 39 178 45.31 180 86.74 46 34 181 36.39 183 31 63 184 87 48 69 185 36 186 77 46 82 187 43 29 100 189 39.49 55 46 53 190 56 36 73 192 87 47 73 193 51.83 84 38 43 194 45.64 195 35 31 197 32.15 199 48 52 202 33.07

The foregoing description and examples have been set forth merely to illustrate the invention and are not intended to be limiting. Since modifications of the described embodiments incorporating the spirit and substance of the invention may occur to persons skilled in the art, the invention should be construed broadly to include all variations within the scope of the appended claims and equivalents thereof. 

1. A process for preparing a substituted 5,6,7,8-tetrahydro-pyrido[4,3-d]-pyrimidin-2-yl compound corresponding to formula I:

wherein X represents an NR^(2a) group; R¹ represents a —C(═O)—R³ group or a —C(═O)—O—R⁴ group; R^(2a) represents a —C(═O)—R⁵ group or an —S(═O)₂—R⁶ group; R³ represents a linear or branched, unsubstituted or at least monosubstituted, saturated or unsaturated aliphatic group, which may comprise at least one heteroatom as a chain link; an unsubstituted or at least monosubstituted, saturated or unsaturated cycloaliphatic group, which may comprise at least one heteroatom as a ring member, which group may be attached via a linear or branched, unsubstituted or at least monosubstituted alkylene group, which may comprise at least one heteroatom as a chain link; or an unsubstituted or at least monosubstituted aryl or heteroaryl group, which may be attached via a linear or branched, unsubstituted or at least monosubstituted alkylene group; R⁴ represents an unsubstituted or at least monosubstituted aryl or heteroaryl group, which may be attached via a linear or branched, unsubstituted or at least monosubstituted alkylene group; R⁵ represents a linear or branched, unsubstituted or at least monosubstituted, saturated or unsaturated aliphatic group, which may comprise at least one heteroatom as a chain link; an unsubstituted or at least monosubstituted, saturated or unsaturated cycloaliphatic group, which may comprise at least one heteroatom as a ring member, which group may be attached via a linear or branched, unsubstituted or at least monosubstituted alkylene group, which may comprise at least one heteroatom as a chain link or may be fused with an unsubstituted or at least monosubstituted, mono- or polycyclic ring system; an unsubstituted or at least monosubstituted aryl or heteroaryl group, which may be attached via a linear or branched, unsubstituted or at least monosubstituted alkylene, alkenylene or alkynylene group, which may comprise at least one heteroatom as a chain link or may be fused with an unsubstituted or at least monosubstituted, mono- or polycyclic ring system; a —C(═O)—R⁷ group, which may be attached via a linear or branched, unsubstituted or at least monosubstituted alkylene group; a —C(═O)—R⁸ group, which may be attached via a linear or branched, unsubstituted or at least monosubstituted alkylene group, or an —N(H)—C(═O)—O—R⁹ group, which may be attached via a linear or branched, unsubstituted or at least monosubstituted alkylene group, which may comprise at least one —N(H)—C(═O) or at least one —C(═O)—N(H) grouping as a chain link; R⁶ represents an —NR¹⁰R¹¹ group; a linear or branched, unsubstituted or at least monosubstituted, saturated or unsaturated aliphatic group, which may comprise at least one heteroatom as a chain link; an unsubstituted or at least monosubstituted, saturated or unsaturated cycloaliphatic group, which may comprise at least one heteroatom as a ring member, and which may be fused with an unsubstituted or at least monosubstituted mono- or polycyclic ring system, which group may be attached via a linear or branched, unsubstituted or at least monosubstituted alkylene group, which may comprise at least one heteroatom as a chain link or may be bridged with a linear or branched alkylene group; or an unsubstituted or at least monosubstituted aryl or heteroaryl group, which may be attached via a linear or branched, unsubstituted or at least monosubstituted alkylene group or may be fused with an unsubstituted or at least monosubstituted mono- or polycyclic ring system; R⁷ represents a linear or branched, unsubstituted or at least monosubstituted alkyl group, an unsubstituted or at least monosubstituted aryl or heteroaryl group, an unsubstituted or at least monosubstituted, saturated or unsaturated cycloaliphatic group, which may comprise at least one heteroatom as a ring member, which group may be fused with an unsubstituted or at least monosubstituted mono- or polycyclic ring system, or an —NR^(7a)R^(7b) group, wherein R^(7a) and R^(7b), identically or differently, in each case, represent a linear or branched alkyl group, R⁸ represents a linear or branched, unsubstituted or at least monosubstituted alkyl group or an unsubstituted or at least monosubstituted aryl or heteroaryl group, which may be attached by a linear or branched alkylene group, R⁹ represents a linear or branched, unsubstituted or at least monosubstituted alkyl group, an unsubstituted or at least monosubstituted aryl or heteroaryl group, which may be attached via a linear or branched alkylene group, or an unsubstituted or at least monosubstituted, saturated or unsaturated cycloaliphatic group, which may be fused with at least one unsubstituted or at least monosubstituted mono- or polycyclic ring system, R¹⁰ and R¹¹, identically or differently, in each case, represent a linear or branched alkyl group, or a salt thereof, said process comprising: reacting a protected piperidin-4-one corresponding to formula II,

wherein PG represents a protective group, with a dimethoxy-methyl-dimethyl-amine corresponding to formula III

in an organic reaction medium to yield a compound corresponding to formula IV,

and optionally purifying or isolating said compound corresponding to formula IV, and reacting said compound corresponding to formula IV with guanidine corresponding to formula V,

which guanidine corresponding to formula V may be present in the form of a salt, in an organic reaction medium, which step of reacting may include the presence of at least one base, to yield a compound corresponding to formula VI,

and optionally purifying or isolating said compound corresponding to formula VI, and reacting said compound corresponding to formula VI in an organic reaction medium, which may optionally include at least one base or at least one catalyst, with a compound corresponding to the formula R³—C(═O)—X¹ or a compound corresponding to the formula (R³—C(═O))₂O, or reacting said compound corresponding to formula VI with a compound corresponding to the formula R³—C(═O)—OH in an organic reaction medium in the presence of at least one coupling agent, which may include at least one base, or reacting said compound corresponding to formula VI with a compound corresponding to formula R⁴—O—C(═O)—X^(1a) in an organic reaction medium, which may include at least one base, wherein X¹ and X^(1a) in each case denote a leaving group, to yield a compound corresponding to formula VII,

and optionally purifying or isolating said compound corresponding to formula VII, and eliminating the protective group PG to yield a compound corresponding to formula VIII,

or a salt thereof, and optionally purifying or isolating the compound corresponding to formula VIII or the salt thereof and reacting said compound corresponding to formula VIII or the salt thereof with a compound of corresponding to the formula R⁵—C(═O)—X² or (R⁵—C(═O))₂O, in an organic reaction medium, optionally including at least one base or at least one catalyst, or reacting said compound corresponding to formula VIII or the salt thereof with a compound corresponding to the formula R⁶—SO₂—X³, wherein X³ represents a leaving group, in an organic reaction medium, optionally including at least one base, or reacting said compound corresponding to formula VIII or the salt thereof with a compound corresponding to the formula R⁵—COOH, in an organic reaction medium, in the presence of at least one suitable coupling agent, optionally including at least one base, to yield a compound corresponding to formula IX

and optionally purifying or isolating said compound corresponding to formula IX and optionally converting said compound corresponding to formula IX to yield a corresponding salt and optionally purifying or isolating the corresponding salt of said compound corresponding to formula IX, or reacting a piperidin-4-one corresponding to formula X

or a salt thereof, with a compound corresponding to the formula R⁵—C(═O)—X² or (R⁵—C(═O))₂O, wherein X² represents a leaving group, in an organic reaction medium, which may include at least one base or at least one catalyst, or with a compound of corresponding to the formula R⁶—SO₂—X³, wherein X³ represents a leaving group, in an organic reaction medium, which may include at least one base, or with a compound corresponding to the formula R⁵—COOH, in the presence of a suitable coupling agent, and in an organic reaction medium, which may include at least one base, to yield a compound corresponding to formula XI,

and optionally purifying or isolating the compound corresponding to formula XI, and reacting said compound corresponding to formula XI with a dimethoxy-methyl-dimethyl-amine corresponding to formula III

in an organic reaction medium to form a compound corresponding to formula XII,

and optionally purifying or isolating said compound corresponding for formula XII, and reacting said said compound corresponding for formula XII with a guanidine corresponding to formula V,

or a salt thereof, in an organic reaction medium which may include at least one base, to yield a compound corresponding to formula XIII

and optionally purifying or isolating said compound corresponding to formula XIII and reacting said compound corresponding to formula XIII in an organic reaction medium, which may include at least one base or at least one catalyst, with a compound corresponding to the formula R³—C(═O))₂O or with a compound corresponding to the formula R³—C(═O)—X¹, or with a compound corresponding to the formula R³—COOH, in an organic reaction medium which may include at least one base and in the presence of at least one coupling agent, or with a compound corresponding to the formula R⁴—O—C(═O)—Xla in an organic reaction medium, which may include at least one base, wherein X¹ and X^(1a) in each case represent a leaving group, to yield a compound corresponding to formula XIV

and optionally purifying or isolating the compound corresponding to formula XIV and optionally converted compound corresponding to formula XIV to yield a corresponding salt and optionally purifying or isolating the salt of the compound corresponding to formula XIV.
 2. A method of noradrenalin receptor regulation, 5-HT receptor regulation, mGluR5 receptor regulation or batrachotoxin receptor regulation, said method comprising administering to a subject in need thereof a pharmaceutically effective amount of a compound corresponding to formula I:

wherein X represents an NR^(2a) group; R¹ represents a —C(═O)—R³ group or a —C(═O)—O—R⁴ group; R^(2a) represents a —C(═O)—R⁵ group or an —S(═O)₂—R⁶ group; R³ represents a linear or branched, unsubstituted or at least monosubstituted, saturated or unsaturated aliphatic group, which may comprise at least one heteroatom as a chain link; an unsubstituted or at least monosubstituted, saturated or unsaturated cycloaliphatic group, which may comprise at least one heteroatom as a ring member, which group may be attached via a linear or branched, unsubstituted or at least monosubstituted alkylene group, which may comprise at least one heteroatom as a chain link; or an unsubstituted or at least monosubstituted aryl or heteroaryl group, which may be attached via a linear or branched, unsubstituted or at least monosubstituted alkylene group; R⁴ represents an unsubstituted or at least monosubstituted aryl or heteroaryl group, which may be attached via a linear or branched, unsubstituted or at least monosubstituted alkylene group; R⁵ represents a linear or branched, unsubstituted or at least monosubstituted, saturated or unsaturated aliphatic group, which may comprise at least one heteroatom as a chain link; an unsubstituted or at least monosubstituted, saturated or unsaturated cycloaliphatic group, which may comprise at least one heteroatom as a ring member, which group may be attached via a linear or branched, unsubstituted or at least monosubstituted alkylene group, which may comprise at least one heteroatom as a chain link or may be fused with an unsubstituted or at least monosubstituted, mono- or polycyclic ring system; an unsubstituted or at least monosubstituted aryl or heteroaryl group, which may be attached via a linear or branched, unsubstituted or at least monosubstituted alkylene, alkenylene or alkynylene group, which may comprise at least one heteroatom as a chain link or may be fused with an unsubstituted or at least monosubstituted, mono- or polycyclic ring system; a —C(═O)—R⁷ group, which may be attached via a linear or branched, unsubstituted or at least monosubstituted alkylene group; a —C(═O)—R⁸ group, which may be attached via a linear or branched, unsubstituted or at least monosubstituted alkylene group, or an —N(H)—C(═O)—O—R⁹ group, which may be attached via a linear or branched, unsubstituted or at least monosubstituted alkylene group, which may comprise at least one —N(H)—C(═O) or at least one —C(═O)—N(H) grouping as a chain link; R⁶ represents an —NR¹⁰R¹¹ group; a linear or branched, unsubstituted or at least monosubstituted, saturated or unsaturated aliphatic group, which may comprise at least one heteroatom as a chain link; an unsubstituted or at least monosubstituted, saturated or unsaturated cycloaliphatic group, which may comprise at least one heteroatom as a ring member, and which may be fused with an unsubstituted or at least monosubstituted mono- or polycyclic ring system, which group may be attached via a linear or branched, unsubstituted or at least monosubstituted alkylene group, which may comprise at least one heteroatom as a chain link or may be bridged with a linear or branched alkylene group; or an unsubstituted or at least monosubstituted aryl or heteroaryl group, which may be attached via a linear or branched, unsubstituted or at least monosubstituted alkylene group or may be fused with an unsubstituted or at least monosubstituted mono- or polycyclic ring system; R⁷ represents a linear or branched, unsubstituted or at least monosubstituted alkyl group, an unsubstituted or at least monosubstituted aryl or heteroaryl group, an unsubstituted or at least monosubstituted, saturated or unsaturated cycloaliphatic group, which may comprise at least one heteroatom as a ring member, which group may be fused with an unsubstituted or at least monosubstituted mono- or polycyclic ring system, or an —NR^(7a)R^(7b) group, wherein R^(7a) and R^(7b), identically or differently, in each case, represent a linear or branched alkyl group, R⁸ represents a linear or branched, unsubstituted or at least monosubstituted alkyl group or an unsubstituted or at least monosubstituted aryl or heteroaryl group, which may be attached by a linear or branched alkylene group, R⁹ represents a linear or branched, unsubstituted or at least monosubstituted alkyl group, an unsubstituted or at least monosubstituted aryl or heteroaryl group, which may be attached via a linear or branched alkylene group, or an unsubstituted or at least monosubstituted, saturated or unsaturated cycloaliphatic group, which may be fused with at least one unsubstituted or at least monosubstituted mono- or polycyclic ring system, R¹⁰ and R¹¹, identically or differently, in each case, represent a linear or branched alkyl group, or a pharmaceutically acceptable salt thereof.
 3. The method of claim 2, wherein said method is effective for inhibiting noradrenalin reuptake or for inhibiting 5-hydroxy-tryptophan reuptake.
 4. A method of treating or inhibiting a condition mediated at least in part by at least one receptor selected from the group consisting of noradrenalin-receptors, 5-HT receptors, mGluR5 receptors and batrachotoxin receptors, said method comprising administering to a subject in need thereof a pharmaceutically effective amount of a compound corresponding to formula I:

wherein X represents an NR^(2a) group; R¹ represents a —C(═O)—R³ group or a —C(═O)—O—R⁴ group; R^(2a) represents a —C(═O)—R⁵ group or an —S(═O)₂—R⁶ group; R³ represents a linear or branched, unsubstituted or at least monosubstituted, saturated or unsaturated aliphatic group, which may comprise at least one heteroatom as a chain link; an unsubstituted or at least monosubstituted, saturated or unsaturated cycloaliphatic group, which may comprise at least one heteroatom as a ring member, which group may be attached via a linear or branched, unsubstituted or at least monosubstituted alkylene group, which may comprise at least one heteroatom as a chain link; or an unsubstituted or at least monosubstituted aryl or heteroaryl group, which may be attached via a linear or branched, unsubstituted or at least monosubstituted alkylene group; R⁴ represents an unsubstituted or at least monosubstituted aryl or heteroaryl group, which may be attached via a linear or branched, unsubstituted or at least monosubstituted alkylene group; R⁵ represents a linear or branched, unsubstituted or at least monosubstituted, saturated or unsaturated aliphatic group, which may comprise at least one heteroatom as a chain link; an unsubstituted or at least monosubstituted, saturated or unsaturated cycloaliphatic group, which may comprise at least one heteroatom as a ring member, which group may be attached via a linear or branched, unsubstituted or at least monosubstituted alkylene group, which may comprise at least one heteroatom as a chain link or may be fused with an unsubstituted or at least monosubstituted, mono- or polycyclic ring system; an unsubstituted or at least monosubstituted aryl or heteroaryl group, which may be attached via a linear or branched, unsubstituted or at least monosubstituted alkylene, alkenylene or alkynylene group, which may comprise at least one heteroatom as a chain link or may be fused with an unsubstituted or at least monosubstituted, mono- or polycyclic ring system; a —C(═O)—R⁷ group, which may be attached via a linear or branched, unsubstituted or at least monosubstituted alkylene group; a —C(═O)—R⁸ group, which may be attached via a linear or branched, unsubstituted or at least monosubstituted alkylene group, or an —N(H)—C(═O)—O—R⁹ group, which may be attached via a linear or branched, unsubstituted or at least monosubstituted alkylene group, which may comprise at least one —N(H)—C(═O) or at least one —C(═O)—N(H) grouping as a chain link; R⁶ represents an —NR¹⁰R¹¹ group; a linear or branched, unsubstituted or at least monosubstituted, saturated or unsaturated aliphatic group, which may comprise at least one heteroatom as a chain link; an unsubstituted or at least monosubstituted, saturated or unsaturated cycloaliphatic group, which may comprise at least one heteroatom as a ring member, and which may be fused with an unsubstituted or at least monosubstituted mono- or polycyclic ring system, which group may be attached via a linear or branched, unsubstituted or at least monosubstituted alkylene group, which may comprise at least one heteroatom as a chain link or may be bridged with a linear or branched alkylene group; or an unsubstituted or at least monosubstituted aryl or heteroaryl group, which may be attached via a linear or branched, unsubstituted or at least monosubstituted alkylene group or may be fused with an unsubstituted or at least monosubstituted mono- or polycyclic ring system; R⁷ represents a linear or branched, unsubstituted or at least monosubstituted alkyl group, an unsubstituted or at least monosubstituted aryl or heteroaryl group, an unsubstituted or at least monosubstituted, saturated or unsaturated cycloaliphatic group, which may comprise at least one heteroatom as a ring member, which group may be fused with an unsubstituted or at least monosubstituted mono- or polycyclic ring system, or an —NR^(7a)R^(7b) group, wherein R^(7a) and R^(7b), identically or differently, in each case, represent a linear or branched alkyl group, R⁸ represents a linear or branched, unsubstituted or at least monosubstituted alkyl group or an unsubstituted or at least monosubstituted aryl or heteroaryl group, which may be attached by a linear or branched alkylene group, R⁹ represents a linear or branched, unsubstituted or at least monosubstituted alkyl group, an unsubstituted or at least monosubstituted aryl or heteroaryl group, which may be attached via a linear or branched alkylene group, or an unsubstituted or at least monosubstituted, saturated or unsaturated cycloaliphatic group, which may be fused with at least one unsubstituted or at least monosubstituted mono- or polycyclic ring system, R¹⁰ and R¹¹, identically or differently, in each case, represent a linear or branched alkyl group, or a pharmaceutically acceptable salt thereof.
 5. A method according to claim 4, wherein said condition comprises pain in a mammal, said method comprising administering to said mammal an effective pain alleviating amount of said compound corresponding to formula I.
 6. A method according to claim 4, wherein said condition is selected from the group consisting of migraine, depression, urinary incontinence, coughing, neurodegenerative diseases, food intake disorders, cognitive dysfunction, cognitive deficiency states, disorders of the nervous system, epilepsy, schizophrenia, cerebral ischaemia, muscle spasms, cramps, diarrhea, pruritus, gastro-oesophageal reflux syndrome, panic attacks, alcohol or drug abuse or abuse of medicines, alcohol or drug dependency or dependency on medicines, withdrawal symptoms associated with alcohol or drug dependency or dependency on medicines, tolerance to medicines, locomotor activity disorders, irregularaties of the cardiovascular system, pain, anxiety, decreased vigilance, decreased libido, diuresis, and antinatriuresis, said method comprising administering to a subject in need thereof a pharmaceutically effective amount of said compound corresponding to formula I.
 7. A method according to claim 6, wherein said condition is a neurodegenerative disease selected from the group consisting of Parkinson's disease, Huntington's chorea, Alzheimer's disease and multiple sclerosis; or a food intake disorder selected from the group consisting of bulimia, anorexia, obesity and cachexia; or a cognitive memory disorder; or a tolerance opioids.
 8. A method of preparing a pharmaceutical formulation for noradrenalin receptor regulation, for 5-HT receptor regulation, for mGluR5 receptor regulation or for batrachotoxin receptor regulation comprising combining a pharmaceutically effective amount of a compound corresponding to formula I:

wherein X represents an NR^(2a) group; R¹ represents a —C(═O)—R³ group or a —C(═O)—O—R⁴ group; R^(2a) represents a —C(═O)—R⁵ group or an —S(═O)₂—R⁶ group; R³ represents a linear or branched, unsubstituted or at least monosubstituted, saturated or unsaturated aliphatic group, which may comprise at least one heteroatom as a chain link; an unsubstituted or at least monosubstituted, saturated or unsaturated cycloaliphatic group, which may comprise at least one heteroatom as a ring member, which group may be attached via a linear or branched, unsubstituted or at least monosubstituted alkylene group, which may comprise at least one heteroatom as a chain link; or an unsubstituted or at least monosubstituted aryl or heteroaryl group, which may be attached via a linear or branched, unsubstituted or at least monosubstituted alkylene group; R⁴ represents an unsubstituted or at least monosubstituted aryl or heteroaryl group, which may be attached via a linear or branched, unsubstituted or at least monosubstituted alkylene group; R⁵ represents a linear or branched, unsubstituted or at least monosubstituted, saturated or unsaturated aliphatic group, which may comprise at least one heteroatom as a chain link; an unsubstituted or at least monosubstituted, saturated or unsaturated cycloaliphatic group, which may comprise at least one heteroatom as a ring member, which group may be attached via a linear or branched, unsubstituted or at least monosubstituted alkylene group, which may comprise at least one heteroatom as a chain link or may be fused with an unsubstituted or at least monosubstituted, mono- or polycyclic ring system; an unsubstituted or at least monosubstituted aryl or heteroaryl group, which may be attached via a linear or branched, unsubstituted or at least monosubstituted alkylene, alkenylene or alkynylene group, which may comprise at least one heteroatom as a chain link or may be fused with an unsubstituted or at least monosubstituted, mono- or polycyclic ring system; a —C(═O)—R⁷ group, which may be attached via a linear or branched, unsubstituted or at least monosubstituted alkylene group; a —C(═O)—R⁸ group, which may be attached via a linear or branched, unsubstituted or at least monosubstituted alkylene group, or an —N(H)—C(═O)—O—R⁹ group, which may be attached via a linear or branched, unsubstituted or at least monosubstituted alkylene group, which may comprise at least one —N(H)—C(═O) or at least one —C(═O)—N(H) grouping as a chain link; R⁶ represents an —NR¹⁰R¹¹ group; a linear or branched, unsubstituted or at least monosubstituted, saturated or unsaturated aliphatic group, which may comprise at least one heteroatom as a chain link; an unsubstituted or at least monosubstituted, saturated or unsaturated cycloaliphatic group, which may comprise at least one heteroatom as a ring member, and which may be fused with an unsubstituted or at least monosubstituted mono- or polycyclic ring system, which group may be attached via a linear or branched, unsubstituted or at least monosubstituted alkylene group, which may comprise at least one heteroatom as a chain link or may be bridged with a linear or branched alkylene group; or an unsubstituted or at least monosubstituted aryl or heteroaryl group, which may be attached via a linear or branched, unsubstituted or at least monosubstituted alkylene group or may be fused with an unsubstituted or at least monosubstituted mono- or polycyclic ring system; R⁷ represents a linear or branched, unsubstituted or at least monosubstituted alkyl group, an unsubstituted or at least monosubstituted aryl or heteroaryl group, an unsubstituted or at least monosubstituted, saturated or unsaturated cycloaliphatic group, which may comprise at least one heteroatom as a ring member, which group may be fused with an unsubstituted or at least monosubstituted mono- or polycyclic ring system, or an —NR^(7a)R^(7b) group, wherein R^(7a) and R^(7b), identically or differently, in each case, represent a linear or branched alkyl group, R⁸ represents a linear or branched, unsubstituted or at least monosubstituted alkyl group or an unsubstituted or at least monosubstituted aryl or heteroaryl group, which may be attached by a linear or branched alkylene group, R⁹ represents a linear or branched, unsubstituted or at least monosubstituted alkyl group, an unsubstituted or at least monosubstituted aryl or heteroaryl group, which may be attached via a linear or branched alkylene group, or an unsubstituted or at least monosubstituted, saturated or unsaturated cycloaliphatic group, which may be fused with at least one unsubstituted or at least monosubstituted mono- or polycyclic ring system, R¹⁰ and R¹¹, identically or differently, in each case, represent a linear or branched alkyl group, or a pharmaceutically acceptable salt thereof, with at least one physiologically acceptable auxiliary substance, and forming the combined substances into a pharmaceutically administrable dosage form.
 9. A method according to claim 8, wherein said pharmaceutical formulation is effective for inhibiting noradrenalin reuptake or for inhibiting 5-hydroxy-tryptophan reuptake. 